Osteoporosis in Males

Catherine Anastasopoulou; Maxim Barnett; Lorenna  Rodrigues Silva Sombra; Vishnu Garla

Osteoporosis in Males

Author: Catherine Anastasopoulou Author: Maxim J. Barnett Author: Lorenna Rodrigues Silva Sombra Editor: Vishnu V. Garla Updated: 1/22/2025 1:26:24 AM

Introduction

Osteoporosis is a disease of weakened bones caused by low mineral density and distortion of the architecture, predisposing them to low-impact, fragility fractures.[1] This condition is often referred to as the "silent disease," as frequently no manifestations are clinically apparent until a fracture has occurred.[2] Osteoporotic fractures are associated with decreased quality of life, increased morbidity, disabilities, and mortality. Osteoporosis translates to "porous bones" derived from the Greek root word poro, which means porous or passage, and osis, meaning condition.[3] Not until the 1820s, however, did a French pathologist, Jean Lobstein, coin the term osteoporosis as a distinctive medical entity.[4]

Although initially considered a disease of postmenopausal females, the burden of osteoporosis on males is of equal peril. Following a first fracture, men are more likely to experience a subsequent fracture compared to females and are at greater risk for morbidity and mortality.[5] However, males experience a fracture roughly 1 decade later than females.[5] Despite improved awareness of the condition in males, only around 10% of men with a diagnosis of osteoporosis appear to receive appropriate treatment; the disease continues to be underrecognized and mismanaged.[6] Early studies on the identification and management of osteoporosis solely focused on postmenopausal females, resulting in challenges in the clinical understanding of the natural history of the disease in males.

Etiology

Register For Free And Read The Full Article

Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.

Search engine and full access to all medical articles
10 free questions in your specialty
Free CME/CE Activities

Free daily question in your email
Save favorite articles to your dashboard
Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Etiology

Osteoporosis is classified into primary and secondary disease, with the latter accounting for up to 60% of cases in men.[7][8] An estimated 20% of older osteoporotic men have hypogonadism.[9] However, primary etiologies are often underestimated due to less active surveillance and screening in patients without typical risk factors. Primary osteoporosis can be further subcategorized into involutional, which refers to individuals older than 70 without an obvious risk factor, and idiopathic, which refers to patients younger than 70 with no obvious risk factor.[10] Categorization can also be based on modifiable and nonmodifiable risk factors.

The causes of secondary osteoporosis are multifold, eg, hypogonadism (including age-related and androgen deprivation therapy types), excess alcohol consumption, corticosteroid excess (exogenous administration or endogenous), malabsorptive states (eg, inflammatory bowel disease, celiac disease, and postgastric bypass surgery), hyperparathyroidism (primary or secondary with associated chronic kidney disease), medication-related (including but not limited to anticonvulsants, chemotherapeutic, antidiabetic agents), and systemic ailments (eg, amyloidosis).[11] (see Table. Conditions Associated With Osteoporosis) Uniquely, diabetes has recently been demonstrated as an osteoporosis and subsequent fracture risk factor despite a relatively normal or even elevated bone mineral density (BMD).[12]

Table. Conditions Associated With Osteoporosis

Lifestyle Factors	Endocrine	Gastrointestinal	Genetic	Rheumatologic/Connective Tissue	Medication	Hematologic	Miscellaneous
Smoking	Hyperparathyroidism	Celiac disease	Hypophosphatasia	Osteogenesis imperfecta	Heparin	Multiple myeloma	Chronic kidney disease
Anorexia nervosa	Hyperthyroidism	Inflammatory bowel disease	Parental history of hip fracture	Ehlers-Danlos	Lithium	Chronic hemolytic anemia	Chronic obstructive pulmonary disease
Vitamin D deficiency	Diabetes	Cirrhosis	Homocystinuria	Marfan syndrome	Glucocorticoids	Systemic mastocytosis	Congestive heart failure
Prior fracture	Delayed puberty	Malabsorption	Cystic fibrosis	Rheumatoid arthritis	Opiates	Haemophilia	Multiple sclerosis
Vitamin A toxicity	Hypogonadism (primary and secondary)	Pancreatic disease	Glycogen storage disease	Systemic lupus erythematosus	Aromatase inhibitors	Lymphoma	Chronic metabolic acidosis
Low calcium Iitake	Hyperprolactinemia	Primary biliary cholangitis	Menkes kinky hair syndrome	Muscular dystrophy	Cyclosporine	Sickle cell disease	HIV/AIDS
High salt intake	Panhypopituitarism	Gastrointestinal surgery	Gaucher disease	Idiopathic scoliosis	Gonadotrophin-releasing hormone agonists	Thalassemia	Posttransplant
Aluminum (antacids)	Amenorrhea	Gastric bypass	Riley-Day syndrome	Sarcoidosis	Anticonvulsants (Phenytoin)	Leukaemia
Inactive/immobilization	Cushing syndrome	Parenteral nutrition	Androgen insensitivity		Barbiturates	Amyloidosis
High caffeine intake	Adrenal insufficiency		Porphyria		Tacrolimus
Excessive alcohol	Hypercalciuria		Hemochromatosis		Thyroxine
Falls	Growth hormone deficiency		Klinefelter syndrome		HIV medication (Tenofovir)
Low body mass index			Turner syndrome		Canagliflozin
					Thiazolidinediones

Epidemiology

An estimated 200 million people, corresponding to around 20% of the global population, hold a diagnosis of osteoporosis.[13] In 2000, around 9 million osteoporotic fractures occurred worldwide, with 39% occurring in men (30% hip, 20% forearm, 42% vertebral, and 25% humerus).[14] In the year 2010, an estimated 8.2 million women and 2.0 million men in the United States were living with osteoporosis.[15] The National Health and Nutrition Examination Survey (NHANES) study initially performed in 1988 to 1994 evaluated hip bone density for men and women older than 50, noting a prevalence of hip osteoporosis of 2% for men and 16% for women.[16] In contrast, the NHANES study from 2005 to 2008 evaluated both hip and vertebral bone density, noting a diagnosis of osteoporosis in 4% of males and 16% of females; this suggested that the osteoporosis diagnosis had doubled for men while remaining relatively unchanged for women. [CDC Nutrition Survey] A further NHANES study performed between 2017 and 2018 demonstrated a prevalence of osteoporosis of around 12.6% of the adult population in the United States above 50 years of age (4.4% male, 19.6% female).[Osteoporosis in Older Adults] The age-related increase in osteoporosis prevalence is suggested to occur at differing magnitudes and ages; in women, the diagnosis of osteoporosis roughly triples at age 70 years, whereas in men, the rate roughly doubles at age 80.[13] It has been estimated that women aged 50 years or older have a 4-fold higher rate of osteoporosis compared with men.[13] Approximately 1 in 3 females and 1 in 5 males older than 50 will have an osteoporotic fracture in their lifetime; however, this is dependent on multiple factors, including race, ethnicity, geography, and underlying clinical disease processes.[17]

The prevalence of osteoporosis amongst non-white groups is limited, however, data from NHANES note a greater prevalence of osteoporosis in non-Hispanic, white men compared to non-Hispanic, black men.[14] It has also been noted that white men have a lower bone mineral density (based on imaging) compared to black men, which remains significant after adjustment for body size.[14] While black males have a lower overall incidence of osteoporosis, once they are diagnosed, their fracture risk is equivocal to that of white males.[14] Although Asian men appear to have either the same or slightly lower bone density as white men, the incidence of hip fractures is noted to be lower in the Asian cohort.[14]

There appears to be a bimodal distribution of fractures amongst men, peaking in adolescence and returning with advancing age. Men are more likely to sustain fractures at younger ages than women; however, this is not due to underlying bone fragility but rather due to a greater likelihood of high-energy trauma. After 50 years of age, women demonstrate a greater incidence of fractures.[14] After age 75, both women and men demonstrate increased fracture rates, though this is more apparent in females.[14] The prevalence of hip fractures in older men is around one-third that of women (5% to 6% compared to 16% to 18%, respectively).[18] Although the prevalence of osteoporosis is higher in women than men, around 30% of all hip fractures (and 40% of all fractures) occur in men, with an increasing incidence due to longevity and greater detection.[6][19] Men lose around 1% of bone mineral density per year and are more likely to experience a fracture around 10 years later than most women, with the greatest risk around 75 years of age.[13][14]

Osteoporotic hip fractures account for the greatest morbidity and mortality in men; it appears that the risk is relatively uncommon until age 75, at which point the risk exponentially rises.[14] In the United States, the ratio of hip fractures in females to males in whites is around 2.9:1 and is estimated to be lower in Asia, around 2.5:1.[14] It has been estimated that by 2050, 1.8 million men globally will suffer from a hip fracture (other estimates suggest this could be as high as 6.8 million), with around a 310% increase in hip fractures between 1990 and 2050 in men.[6][14]

Vertebral fractures are underestimated, as they can be silent and incidentally noted on radiological imaging for alternative purposes. In the European Vertebral Osteoporosis Study, men demonstrated a greater incidence of vertebral deformities younger than 65; however, women demonstrated a greater incidence at ages older than 65.[20] The European Prospective Osteoporosis Study demonstrated an age-standardized incidence of vertebral fractures of 5.7 per 1,000 person-years in men versus 10.7 per 1,000 person-years in women, showing a near double risk in females.[21] In a 10-year study including the participants from the European Vertebral Osteoporosis Study cohort in Sweden, it was demonstrated that vertebral deformities were a predictor of mortality in men for the next decade (age-adjusted hazard ratio 1.4; 95% CI 1.6-3.9).[14][22]

Compared to females, the incidence of nonvertebral, nonhip osteoporotic fractures in men (eg, distal radius fractures) appears relatively stable with aging; the risk of a Colle's fracture is a sixth of that of females (2.5% compared to 16%).[14][23] However, men older than 40 with a distal forearm fracture demonstrated a hazard ratio of 2.27 for an ensuing hip fracture (95% CI 1.15-4.5).[14][24]

Pathophysiology

Bone mineral density (BMD) is expressed by the mass of calcium hydroxyapatite present in a given area (g/cm²) or volume (g/cm³) of bone.[25] Peak bone mass, therefore, refers to the total amount of bone tissue at the end of skeletal maturation.[26] No evidence of a gender-related difference in bone mass has been identified in newborns.[27] The similarity in bone mass in both genders is consistent until the beginning of puberty.[28] The increase in bone mass starts on average 2 years earlier in females compared to males.[29] During puberty, periosteal bone formation is more significant in males, resulting in increased cortical width, whereas females have less periosteal bone formation but more endocortical apposition. The increased androgens in males, as well as growth hormone and insulin-like growth factor 1 (IGF-1), additively stimulate the apposition of periosteal bone in men, whereas estrogens inhibit periosteal apposition in females, culminating in wider bones in men compared to women.[30]

The 2 most important considerations for bone density in an individual include peak bone mass and the rate of bone loss. Decreased bone mass may result from a reduction in pubertal bone growth or the acceleration of bone resorption following attainment of peak bone mass; both of these processes, to varying degrees, may likely be associated with osteoporosis in the individual male patient.[6][14] The peak BMD is up to 10% higher in males than females; therefore, males have greater peak bone mass before the acceleration of bone resorption.[6] Women demonstrate a younger onset of bone loss compared to men and undergo more rapid bone loss.[13] Peak bone mass acquisition typically occurs around the third decade but can vary based on genetic, hormonal, and environmental factors.[31]

In men, BMD increases exponentially during puberty as a response to the production of sex steroids; much of the increase (predominantly for cortical bone) is due to an increase in bone size.[32] Sex steroids are vital in attaining peak bone mass; in men with idiopathic hypogonadotropic hypogonadism who do not undergo puberty (unless treated appropriately), both cortical and trabecular bone density is reduced, even during periods of rapid bone accrual before peak adult BMD.[33][34] Furthermore, androgens and estrogens are important in peak bone mass acquisition; in males with mutations with complete insensitivity to either hormone receptor, BMD is notably reduced. Another component for peak bone density is the timing or onset of puberty; in those with constitutionally delayed puberty, BMD of the lumbar spine, proximal femur, and radius are all significantly lowered, and even with restoration of sex steroid production, BMD does not normalize.[35][36]

Following peak bone mass, both men and women usually start bone loss in the middle of the 3rd decade; however, while it accelerates following menopause in females, bone loss is more gradual in males.[37] Around 20% of cortical bone and 30% of trabecular bone will be lost in men over their lifetime; trabecular bone is lost shortly after attaining peak BMD, whereas a delay is present before cortical bone is lost.[8][37] Age-related bone loss acceleration, therefore, can occur from increased resorption or if bone formation is impaired during the remodeling of the skeleton. The Dubbo Osteoporosis Epidemiological Study demonstrated an annual bone loss of 0.82% per year for men and 0.96% per year for women at the femoral neck.[38] Moreover, the Framingham Osteoporosis Study noted an average 4-year bone loss of 0.2% to 3.6% for men and 3.4% to 4.8% for women at the hip, lumbar spine, and radius.[39] As mentioned, bones are typically larger in men than in women, providing mechanical advantages and protection from stressors, distributing across a greater surface area.[40] With aging, the external diameter of the bone appears to increase more in men than in women, most likely from androgenic action upon periosteal apposition.[6] Furthermore, men have more bone trabeculae than women. In men, aging is associated with trabecular thinning (but not loss), whereas in women, aging is associated with perforations and trabecular bone loss.[6]

Contrary to women, where following menopause, a rapid reduction in estrogen levels occurs, a less abrupt change occurs in males, and most men can maintain normal androgen levels throughout their lives.[6] Although infrequent, an accelerated process can occur in men, more commonly in those older than 70.[6] Whether gonadal steroids play a role in age-related bone loss is less apparent. In certain situations with pursuant hypogonadism, eg, from an acute illness or commencement of medication (leading to a sudden reduction in testosterone levels), increased resorption of bone may occur, with rapid loss and risk of fractures similar to postmenopausal women not on estrogen therapy.[6] That aging can lead to a reduction in sex hormone-binding globulin is well established, which can reduce free testosterone levels.[14] The Osteoporotic Fractures in Men Study (MrOS) analyzed over 2,000 men older than 65, noting that the prevalence of osteoporosis at either the hip or rapid hip bone loss was around 3-fold greater in men with total testosterone under 200 ng/dL.[41] However, the relationship between estrogen and bone density appears to be more robust than androgens.[42] As mentioned previously, MrOS demonstrated progressive increases in the diagnosis of hip osteoporosis as either bioavailable or total estrogen declined.[6][43] Furthermore, low estradiol was noted to be a predictor of future hip fractures in men; the risk for fracture appeared to be even more significant with concomitant low testosterone.[43] Multiple studies have demonstrated that the regulation of bone turnover in men is primarily accomplished by estrogen, with a small risk of hypogonadal bone loss in men until estradiol levels are below 10 pg/mL and testosterone is below 200 ng/dL.[44] However, the main source of estradiol in men is the aromatization of testosterone.[45] In iatrogenic hypogonadism, eg, in men with prostate cancer who receive GnRH analogs (that lead to testosterone levels of zero and significantly lower estradiol), they have more profound bone loss compared to those on androgen receptor blockers (and subsequently normal estradiol levels).[42][46]

Apart from the osseous effects, androgens are important in preserving muscle mass; in males with a progressive decline with aging, sarcopenia may develop, which can furthermore contribute to an increased risk for falls. Certain studies have demonstrated that older men with sarcopenia are more likely to demonstrate densitometric osteoporosis compared to men with relatively normal appendicular skeletal muscular mass.[47]

The exact underlying pathology of age-related (idiopathic) osteoporosis in men is unclear, though the cause may be associated with low levels of IGF-1 without abnormalities in growth hormone.[14]

Histopathology

The histopathology of osteoporosis is characterized by contraction and loss of trabeculae, alongside decreased osteon sizes and enlargement of the Haversian canals within compact bone and marrow spaces.[48]

History and Physical

Clinical History

While investigating men with osteoporosis, inquiring about calcium and vitamin D intake, sun exposure, prior fractures and associated mechanism of trauma, as well as history of height loss is essential. The following information should be elicited in a systematic way to aid in identifying a secondary or reversible cause of osteoporosis and exclude differential diagnoses:

Medications: Use of medications including anticonvulsants, chemotherapeutics, glucocorticoids, cyclosporin, tacrolimus, aromatase inhibitors, GnRH agonists, levothyroxine suppressive therapy (eg, post thyroid cancer), HIV medications, and long term heparin. Long-term opioid use can also indirectly cause osteoporosis by provoking hypogonadism.
Endocrine causes: Hyperthyroidism, exogenous or endogenous hypercortisolism, hyperparathyroidism, hypogonadism, type 1 or type 2 diabetes, vitamin D deficiency or resistance, delayed puberty, androgen insensitivity, and growth hormone deficiency
Malabsorption: Celiac disease, postbariatric surgery, inflammatory bowel disease
Hematologic causes: Multiple myeloma, systemic mastocytosis, chronic hemolytic anemia
Connective tissue diseases: Osteogenesis imperfecta, Marfan syndrome, Ehlers-Danlos syndrome, and hereditary hypophosphatemic rickets
Miscellaneous: chronic liver disease, chronic kidney disease, hypercalciuria, anorexia nervosa, chronic obstructive pulmonary disease, rheumatoid arthritis, malignancy, and organ transplantation [49]

Additionally, obtaining a complete social history inquiring about smoking, alcohol abuse, and a sedentary lifestyle is essential.[50]

Physical Examination

The physical examination in a patient with primary osteoporosis is usually unremarkable unless an advanced disease is present, for which patients may present with kyphosis and reduced height from prior measured height if a previous compression vertebral fracture had occurred. A general physical exam should also include an evaluation of gait, balance, mobility, overall frailty, muscle mass, signs of secondary osteoporosis (eg, testicular atrophy), signs of thyrotoxicosis, evidence of exogenous medication administration, and signs of chronic obstructive pulmonary disease.[50] Furthermore, if anticipating therapy, assessing dental hygiene before starting treatment is obligatory to rule out jaw osteonecrosis.

Evaluation

Recommendations for Screening

The Endocrine Society recommends BMD testing in all men 70 years or older and men aged 50 to 69 years if risk factors are present; these recommendations are concurred by the International Society for Clinical Densitometry (ISCD) and the National Osteoporosis Foundation, amongst others.[50][51] The Canadian Osteoporosis Society advises BMD testing for all men older than 65 years. However, the United States Preventative Services Task Force (USPSTF) notes insufficient evidence for screening for osteoporosis in men.[52][53]

The Endocrine Society recommends performing a dual-energy x-ray absorptiometry (DEXA) scan of the spine and hip in men at risk for osteoporosis, and the forearm DEXA scan (a one-third portion of the dominant radius) is recommended when the lumbar spine or hip BMD cannot be reliably interpreted as well as for men with hyperparathyroidism or on androgen deprivation therapy.[50] Overall, the proximal femur is less likely to have degenerative changes than the lumbar spine, which can risk a false increase in bone densitometry measurement. A caveat, however, is that spinal BMD has less intermeasurement variability and will detect response to treatment earlier than at the hip.[54][55]

Osteoporosis Diagnosis

A diagnosis of osteoporosis in men older than 50 years of age can be made with a history of a fragility fracture or in those whose BMD T-score is ≤-2.5 standard deviations (SD).[50] Notably, the use of bone densitometry is less standardized in men than in postmenopausal women. However, the correlation between BMD and fracture risk is similar amongst men older than 50 years old and postmenopausal women. Therefore, WHO uses similar thresholds for the diagnosis of osteoporosis in both groups.[50] Both the ISCD and WHO endorse a young female reference database to calculate T-scores in men; however, clinicians should be aware that many institutions may use a sex-specific reference database. The latter approach of using sex-specific database ranges is preferred, as many trials assessing treatment in males with osteoporosis used T-scores calculated using normal male controls.[56] In men younger than 50, BMD is insufficient for diagnosis of osteoporosis, and a diagnosis requires a Z-score of ≤-2.0 SD in addition to a major risk factor or history of fragility fracture.[50]

Other Imaging Studies

Although the DEXA scan is the most commonly used test for assessing BMD, other methods are available (see Table. Imaging Studies for Bone Mass Density Assessment).[50][57][58][59][60][61][62]

Table. Imaging Studies for Bone Mass Density Assessment

Quantitative Heel Ultrasound	This does not measure bone BMD but calculates a stiffness index. While this is more convenient, with the benefits of portability and no radiation exposure, it has not been demonstrated to reduce fracture risk and cannot be used to monitor therapy. Moreover, without BMD, the patient cannot be classified according to the WHO diagnostic classification.
Quantitative Computed Tomography	This measures the volumetric density of bone in the spine and hip and can analyze the cortical and trabecular bones separately. However, it is not currently recommended for screening as it is expensive, has not been validated for fracture risk, and provides greater radiation exposure.
Peripheral DEXA	This portable instrument provides BMD measurements at the finger, calcaneus, and forearm. It carries a risk of technical error and subsequent determination of fracture risks. Furthermore, standardized references are lacking.
Trabecular Bone Score	This FDA-approved add-on software for DEXA systems assesses fracture risk and monitors ongoing therapy. It cannot diagnose osteoporosis or initiate therapy.
Vertebral Fracture Assessment	In patients with osteopenia or osteoporosis who might have had undiagnosed vertebral fractures, thoracic and lumbar spine imaging should be obtained by vertebral fracture assessment (VFA). It has lower cost and radiation exposure than regular plain radiographs and can be obtained simultaneously as the DEXA scan. The ISCD recommends VFA for men older than 80 with osteopenia, younger men with historical height loss (>6 cm), and younger men (aged 70 to 79) with chronic diseases, eg, Crohn's disease, rheumatoid arthritis, or chronic obstructive pulmonary disease.
Lateral Spine Radiography	If VFA and DEXA scanning is unavailable, then lateral spine radiographs should be obtained. Lateral spine radiography should also be considered in the following patients: In men aged 80 and older, if BMD T-score is ≤−1.0 Men of any age with specific risk factors: Low-trauma fracture during adulthood (age 50 and older) historical height loss of 1.5 inches (4 cm) or more when compared to peak height at age 20 Prospective height loss of ≥0.8 inches (2 cm) with previously documented height Recent or current long-term glucocorticoid treatment

Laboratory Evaluation

Initial laboratory evaluation for males with osteoporosis should include serum calcium, phosphate, creatinine with estimated glomerular filtration rate, alkaline phosphatase, liver function, 25(OH)vitamin D, total testosterone, complete blood count, and 24-hour urinary calcium, including creatinine and sodium. If a specific cause of osteoporosis is suggested by history and physical exam, a more thorough investigation can be pursued, including free testosterone, prolactin, IGF-1, serum protein electrophoresis with free and light chains or urine protein electrophoresis, tissue transglutaminase antibodies, thyroid function tests, and parathyroid (PTH) levels. Note that the list of secondary causes of osteoporosis is extensive, and the laboratory investigation needs to follow clinical suspicion.[50] Biochemical markers of bone turnover can also be checked at baseline to aid in risk assessment, serve as an additional monitoring tool when treatment is initiated, and assess compliance with treatment. However, their role in individual patients is not well established.[50]

Treatment / Management

Indications for Treatment

Following the Endocrine Society guidelines, treatment indications for males include the following:

Men with osteoporotic fractures
Men without osteoporotic fractures with a BMD of the femoral neck, spine, or total hip ≥-2.5 SD below the mean for a young, healthy white male
Men receiving long-term corticosteroid therapy (prednisone equivalent or higher than 7.5mg per day for more than 3 months duration)
Men with a T-score between -1.0 and -2.5 in the total hip, femoral neck, or spine with a 10-year risk of >20% for any fracture or a 10-year risk for hip fracture >3% using the FRAX score [50]

(A1)

Nonpharmacologic Management

The following lifestyle and dietary modifications are recommended as part of osteoporosis treatment:

Smoking: Fracture risk is increased in both current and former cigarette smokers; however, the risk is heightened with current smokers. One meta-analysis specifically assessing smoking and fracture risk in men demonstrated a relative risk of 1.37 (95% CI: 1.22-1.53).[63] Prior studies have shown a 32% increased risk of spine fractures and a 40% increased risk of hip fractures in male smokers.[64] The underlying pathophysiology is not entirely understood, but it is believed to be a combination of nicotine and cadmium effects upon bone tissue, reduction of calcium absorption, vitamin D deficiency, and interference with tissue repair processes.[63]
Diet: Balanced diet with adequate protein and dairy intake.
Physical activity: Regular physical activity, at least 30 to 40 minutes of weight-bearing exercises 3 to 4 times per week, is recommended. Numerous studies demonstrated the reduction of osteoporotic fractures in men with physical activity.[50] Examples include:
- The PASSWORD study: Moderate-to-vigorous physical activity was associated with a smaller decline (4 mg/cm2) in BMD of the femoral neck.[65]
- The UK BioBank study: Leisure physical activity was associated with a lower osteoporosis risk (OR 0.83; 95% CI: 0.79-0.86), with consistent protective effects noted upon follow-up.[66]
Alcohol consumption: Reducing alcohol intake is essential. The Endocrine Society recommends no more than 2 units of alcohol per day.[50] Data suggest an increased risk of fractures of any type when more than 3 units of alcohol are consumed daily.[67] Estimates suggest that alcohol intake accounts for around 7% of hip fractures in men.[67]
Fall precautions: The National Osteoporosis Foundation (NOF) recommends assessing patients with risk factors for falls and offering appropriate modifications (eg, home safety assessment, physical therapy, correction of vitamin D insufficiency or deficiency, caution with central nervous system depressant medications, avoidance of hypotension, and visual correction).[51]
Vitamin D and calcium: Evidence suggests that the combination of both vitamin D and calcium can reduce fractures in multiple studies. Vitamin D given alone (400-800 IU) shows no effect in reducing fractures.[68] However, there is also some controversial evidence that calcium supplementation can increase cardiovascular disease (CVD) frequency in females and males. The NIH-AARP Diet and Health Study assessed calcium intake at baseline in 388,229 men and women aged 50 to 71. Patients were followed for 12 years, and cardiovascular events were identified. The authors found that men on calcium supplementation had a 20% higher risk of CVD death, which was not true for women.[69] Therefore, the NOF recommends a diet with adequate amounts of total calcium (at least 1000 mg/day for men 50–70 years old and 1200 mg/day for men 71 years and older) and adding calcium supplements only if dietary intake is insufficient. Vitamin D intake (800–1000 IU/day), including supplements if necessary, is also advised for individuals age 50 and older to achieve a vitamin D level of 30 ng/ml or greater.[51]

(A1)

Pharmacologic Management

The Food and Drug Administration (FDA) has approved several antiresorptive medications for treating osteoporosis in males.

Bisphosphonates

Bisphosphonates are synthetic analogs of inorganic pyrophosphate deposited in the bone matrix.[70] Currently, 3 generations of bisphosphonates are available, and 3 are approved for osteoporosis in men, including alendronate, risedronate, and zoledronic acid.[50][70] Meta-analyses have noted a significant reduction in men for both vertebral (RR 0.36; 95% CI: 0.24-0.56) and nonvertebral fractures (RR 0.52; 95% CI: 0.32-0.84). Bisphosphonates are approved for the treatment of primary osteoporosis as well as glucocorticoid-related osteoporosis.[50](A1)

Alendronate 70 mg and risedronate 35 mg tablets must be taken once weekly on an empty stomach with 8 oz of plain water. Patients must wait at least 30 minutes after taking these medications before eating, drinking, or taking any other medication. During that time, they should remain upright, either sitting or standing.[71] Zoledronic acid is given intravenously 5 mg over at least 15 minutes, once a year or every 2 years. Patients may experience flu-like symptoms after first administration, which can be prevented with adequate hydration and pretreatment with acetaminophen.[71] Following a recent hip fracture, the Endocrine Society recommends commencing treatment with zoledronic acid.[50] Moreover, patients with esophageal disease (eg, varices, structures, or achalasia), a history of bariatric surgery, or an inability to comply with the oral administration requirements should also receive intravenous zoledronic acid.(A1)

Adverse effects are class-related and include gastrointestinal problems, eg, gastritis and esophagitis, and hypocalcemia, which must be corrected before starting treatment. All bisphosphonates are contraindicated in patients with an estimated GFR below 30 to 35 mL/min and with untreated vitamin D deficiency. Osteonecrosis of the jaw (ONJ) is a rare adverse effect, more associated with high-dose intravenous bisphosphonate use in patients with cancer.[50] The risk increases with a duration of more than 5 years.[71] Also, rare, low-trauma atypical femur fractures may be associated with long-term use of bisphosphonates.[71] (A1)

Denosumab

Denosumab is a monoclonal antibody that targets RANK-L (Receptor Activator of the Nuclear Factor Kappa-B Ligand); by binding the RANK-L with high affinity, it prevents the ligand from activating its receptor, RANK, on the surfaces of osteoclasts, inhibiting bone resorption.[72] It was approved for use in men with osteoporosis after the study ADAMO, which revealed an increase in BMD of the lumbar spine (8.0%), total hip and femoral neck (3.4%), trochanter (4.6%) and one-third radius (0.7%).[73] The HALT trial furthermore demonstrated a significant reduction in the incidence of new vertebral fractures in men with nonmetastatic prostate cancer receiving androgen deprivation therapy.[74] In males, it is FDA-approved for the treatment of osteoporosis at high risk for fractures with primary osteoporosis and for those with prostate cancer on androgen deprivation therapy who are at high risk of fractures.[50](A1)

Furthermore, denosumab is FDA-approved for men and women at risk for glucocorticoid-induced osteoporosis.[75] Denosumab has to be administered by a health professional, 60 mg every 6 months subcutaneously.[71] It may cause hypocalcemia, which has to be corrected before starting this medication. Denosumab can increase the risk of serious skin infections (cellulitis) and skin rash. Like bisphosphonates, it has also been rarely associated with the development of ONJ, although it is more common when used in patients with cancer at higher doses.[71] Denosumab has also rarely been associated with the development of atypical femur fractures. If chosen to be discontinued, another agent should be promptly initiated since rapid bone loss has been shown to happen very soon after discontinuation.[76](A1)

Teriparatide

Teriparatide is a recombinant human PTH 1-34 synthetic polypeptide with a similar sequence of the amino acids 1-34 of the amino-terminal region of the endogenous human PTH (PTH 1-84), the biological action sequence.[77] It binds with similar affinity to the G protein-coupled receptor because it is identical to the biologically active fraction of PTH 1-84.[78] The FDA has approved it for the treatment of osteoporosis in men at high risk for fractures.[50] Teriparatide is also approved for treatment in men with glucocorticoid-related osteoporosis with a high risk for fractures.[79] Strong evidence of the efficacy of teriparatide in increasing BMD and reducing vertebral and nonvertebral fractures in postmenopausal women has been documented. A follow-up observational study of male patients who participated and were treated with teriparatide showed those patients had fewer vertebral fractures; however, the evidence regarding nonvertebral (primarily hip) fractures was inconsistent.[80][81] (A1)

Teriparatide is administered as a 20 μg daily subcutaneous injection; previously, there was a duration limit of 24 months due to concern for the risk of osteosarcoma; however, in November 2020, the US FDA removed the 24-month limit and the boxed warning of osteosarcoma. This decision to remove the 24-month limit is multifold; firstly, the studies demonstrating an increased risk were performed in rats, with a dosage 3 times that used in humans.[82] Additionally, after 18 years of postmarketing surveillance, there did not appear to be an increased risk of osteosarcoma amongst those treated with 2 years of teriparatide.[51][82] When treatment is discontinued, bone loss can be rapid, and either bisphosphonates or denosumab should be considered to maintain BMD.[51](A1)

Possible adverse effects are leg cramps, nausea, and dizziness.[79] Teriparatide has shown a dose-dependent increase in the incidence of osteosarcoma in rats (on much higher doses than that used for humans.) Therefore, patients with an increased risk of osteosarcomas, including patients with Paget's disease of bone (PDB), a history of prior radiation therapy of the skeleton, bone metastases, or a history of primary bone malignant tumors should not receive teriparatide if they require treatment for osteoporosis.[79] Patients with PDB and osteoporosis benefit from zoledronic acid for both conditions.[83] Combining teriparatide and a bisphosphonate is not recommended, as it has been demonstrated that the combination of these 2 agents attenuates the stimulus for bone formation promoted by teriparatide.[50] (A1)

Abaloparatide

Abaloparatide (PTHrP 1-34) is a synthetic analog of PTH-related peptide (PTHrP) with 76% homology that binds more selectively than teriparatide to the PTH type 1 receptor (PTH1R). It binds selectively to the RG conformation of that receptor, which confers a more transient response, favoring bone formation and avoiding more prolonged activation and its undesired effects, eg, bone resorption and hypercalcemia.[84][85] It has been available in the United States since 2017 and has proven to be efficacious in postmenopausal women with osteoporosis, reducing the risk of new vertebral and nonvertebral fractures over 18 months in the ACTIVE trial.[86] In men, both the ATOM and ACTIVE-J studies demonstrated an increase in BMD, however, did not address fracture reduction.[87][88] Although evidence for a true reduction in both vertebral and nonvertebral fractures in men is limited, it was FDA-approved in December 2022 for males with osteoporosis and those at high risk for fractures.[89] Abaloparatide is administered as an 80 μg subcutaneous daily injection.[90] Currently, the recommended duration of its use should not exceed 18 months. (A1)

Romosozumab

Romosozumab is a mixed anabolic-antiresorptive monoclonal antibody that binds to and inhibits sclerostin. Osteocytes secrete sclerostin and regulate bone formation. Its inhibition by romosozumab has shown a dual effect on increased bone formation and decreased bone resorption.[91] In 2018, the BRIDGE study demonstrated a significant increase in lumbar spine BMD (12.1%) and total hip BMD (2.5%) in men treated with osteoporosis; a major safety concern was the increase in cardiovascular events in the treatment group (4.9 versus 2.5%).[92] Meta-analyses from the BRIDGE study, which have included both men and women, have noted a reduction in major osteoporotic fractures, but no studies have solely addressed fracture risk reduction in men.(B3)

Currently, the medication has FDA approval only for postmenopausal women with no significant cardiovascular risk. Although it has not been approved for males in the United States, romosozumab is approved for men in Japan and South Korea.[93] Romosozumab is administered subcutaneously at 210 mg every month for a total of 12 months; following completion, switching to bisphosphonates to prevent BMD loss is advised.[94]

Testosterone

Testosterone is the primary therapy in hypogonadal patients, for which it increases bone mineral density and decreases sarcopenia. The Endocrine Society recommends adding either a bisphosphonate or teriparatide to men at high risk of fractures on testosterone therapy with functional hypogonadism (or age-related declines in testosterone levels). This is because data do not support a reduction in fracture risk in men with late-onset functional hypogonadism solely receiving testosterone therapy.[50] In patients at high risk for fractures who have a total testosterone level below 200 ng/dL on more than 1 occasion, in addition to signs or symptoms of androgen deficiency, the Endocrine Society furthermore recommends testosterone treatment in place of alternative bone agents.[50](A1)

Similarly, in men with total testosterone below 200 ng/dL at high risk for fractures who have contraindications to other pharmacologic therapies, the Endocrine Society recommends testosterone therapy.[50] The indications for defining high risk include patients on high-dose glucocorticoids, frequent falls, history of a recent fragility fracture, particularly with a BMD T-score below -2.5 at any skeletal site, T-scores below -3.5 or even below -3.0 if they have other risk factors for fracture, T-score <-2.5 (or fragility fracture) even after receiving adequate testosterone therapy for 2 years.[50] (A1)

Testosterone may be administered in intramuscular, transdermal, or long-acting injectable formulations. Risks regarding the administration of testosterone include sleep apnea, cardiovascular disease, thromboembolism, impaired fertility, breast enlargement, and worsening of preexistent prostatic disease.[95] In 2023, the TRAVERSE study assessed testosterone replacement (gel) in men with hypogonadism, noting no increased risk of cardiovascular events, prostate cancer, or urinary retention. Although a greater risk of fractures was noted, these were predominantly ankle fractures that happened mostly towards the start of treatment, for which the likely etiology is believed to be due to a behavior change.[96][97] (B3)

Calcitonin

Calcitonin is not FDA-approved for osteoporosis in men; however, the Endocrine Society recommends considering unapproved agents such as calcitonin when approved agents cannot be administered.[50] A meta-analysis in 2017 demonstrated a failure of calcitonin to reduce the risk of vertebral fractures in men compared to bisphosphonates.[98] (A1)

Strontium ranelate

Multiple safety concerns exist, such as a heightened risk of thromboembolic events and myocardial infarction, for which the medication is scarcely used.[99] Moreover, Strontium ranelate has not been approved for men with osteoporosis. Like calcitonin, the Endocrine Society recommends only considering this medication when alternative (approved) agents cannot be administered.[50] The MALEO trial 2013 demonstrated that men with treated osteoporosis significantly increased BMD at the lumbar spine, total hip, and femoral neck.[100] (A1)

Sequential Therapy

Sequential monotherapy is preferred when osteoporosis is diagnosed in younger individuals, as patients are more likely to need long-term therapy. As the majority of anti-osteoporotic medications cannot be continued indefinitely, this management is preferred to keep patients covered for the longest period while not increasing the risk of significant adverse effects.

For men with severe osteoporosis at a very high risk for fractures, a common option is to commence an anabolic agent followed by an antiresorptive treatment. To prevent the loss of the newly formed bone, an antiresorptive agent must begin within 1 month of completing the course of anabolic therapy (although bone loss following discontinuation of anabolic treatment appears to be less pronounced in males).[101][102] As noted above, the combination of bisphosphonates and teriparatide is not advised, as the anabolic effect of teriparatide appears to be attenuated.

The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (2023) recommends stratifying patients into "high risk" and "very high risk." Those with high risk may start first-line therapy with an oral bisphosphonate or second-line therapy with denosumab or zoledronic acid; conversely, those at very high risk should be started with an anabolic agent (eg, abaloparatide) followed by an antiresorptive treatment.[1](A1)

Duration of Treatment

No anti-osteoporotic therapy should be considered indefinite. Except for bisphosphonates, all other medications produce effects that wane relatively quickly after discontinuation. In contrast, bisphosphonates retain residual effects following treatment discontinuation.[103] For patients at low risk of fractures on bisphosphonates, stopping zoledronic acid after 3 years and both alendronate/risedronate after 5 years is recommended. In contrast, those at higher risk for fractures are advised to continue zoledronic acid for up to 6 years and alendronate/risedronate for up to 10 years.[104] For patients who continue to have a high risk for fracture, treatment with a bisphosphonate should be resumed after a pause of 1 to 2 years, or alternative therapy should be considered.[105] Denosumab has no strict duration limit; however, if discontinued, there is a rapid rebound with a higher risk of vertebral fractures, for which an additional agent must be commenced. Similarly, abaloparatide (limit of 18 months) and romosozumab (limit of 1 year) must be followed by antiresorptive agents to prevent discontinuation-associated bone loss; teriparatide no longer has a duration limit of 24 months, but after discontinuation, requires transitioning to an antiresorptive agent.(A1)

The Endocrine Society recommends assessing BMD at the spine and hip every 1 to 2 years to evaluate response to treatment.[50] They furthermore recommend decreasing the frequency of DEXA scans if the BMD plateaus. The society additionally recommends considering measuring bone turnover markers at 3 to 6 months after commencing treatment; these may include bone resorption markers on antiresorptive therapy (eg, serum C-terminal telopeptide of type I collagen [CTX] or urine N-terminal telopeptide [NTX]), or bone formation markers for anabolic therapy (eg, serum procollagen type I N-propeptide [PINP]).[50] The International Osteoporosis Foundation and International Federation of Clinical Chemistry have recommended bone-resorptive marker serum CTX and bone formation marker serum P1NP for use in risk prediction for osteoporosis and monitoring response to treatment.[106] The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases (2023) recommends measuring bone turnover markers after 3 months as a method of assessing adherence; a decrease of more than 38% in P1NP and 56% for CTX suggests treatment adherence.[1](A1)

Differential Diagnosis

Differential diagnoses to be considered in a patient with a fragility fracture include:

Vitamin D deficiency (<20 nmol/L) or insufficiency (<30 nmol/L), which can lead to osteomalacia.
Hyperparathyroidism is due to excess parathyroid hormone stimulation upon the bones to release calcium, which increases the risk of fractures.
Hyperthyroidism due to excess catabolism of bone tissue from uncontrolled thyroid hormones.
Paget's disease of the bone is associated with a heightened risk for bone fragility and fractures (occurring in up to 30% of patients).
Osteogenesis imperfecta should be considered in families with a history of recurrent fractures, hearing impairment, and blue sclerae.
Solid tumors with metastases to the bone, commonly from the lung, breast, and prostate.
Hematologic malignancies, eg, multiple myeloma, can invade osseous tissue and predispose to fractures.
Although infrequent, primary bone tumors, eg, osteosarcoma, should be considered in younger individuals.
Avascular necrosis of the femur should be considered with sudden onset pain in the groin or hip region in patients on chronic steroid therapy or with sickle cell disease.

Prognosis

Although the prevalence of osteoporosis is higher in females than in males, the morbidity and mortality after osteoporotic fractures are worse in men than in women.[107] Following a hip fracture, men are twice as likely as women to die in hospital, with a 1-year mortality estimate of around 31% to 35% for men compared to 17% to 22% for women.[108] Moreover, around half of men who experience a hip fracture require institutionalized care, and those who do not require institutionalized care are less likely to be able to return to independent living after 1 year.[109] An estimated 11.5 years of life is lost in men 60 to 69 years of age following a hip fracture; this decreases to 5 years between ages 70 and 79 years and 1.5 years in ages 80 years and older.[14]

Complications

Complications from fractures include pain and discomfort, loss of height (if vertebral), and reduced mobility and independence. There is also an increased risk for falls and future fractures, and more risks from both the surgery and the use of medications.

Consultations

An interprofessional team is often required to manage such patients; teams to consider involved in the patient's direct care include rheumatology, endocrinology, pharmacist, dietitian, orthopedics, geriatrics, radiology, and physical therapy.

Deterrence and Patient Education

Educating and assessing patients is essential to prevent fractures by reducing the risk of falls, eg, wearing appropriate shoes, removing home hazards, lighting up the living space, and using assistive devices. Informing patients about the importance of obtaining calcium from the diet and supplementing with calcium tablets if the required amount can not be obtained from the diet is also vital. All patients should be educated and advised to decrease alcohol consumption, stop smoking, and maintain appropriate physical activity.

Pearls and Other Issues

Key factors to keep in mind when managing osteoporosis in males include:

Osteoporosis in men is a growing problem in the United States and worldwide. The incidence of osteoporosis in males is growing due to multiple factors, including the aging of the population and a more sedentary lifestyle. It is usually overlooked due to previously being considered a postmenopausal female medical problem. However, men experience higher mortality and morbidity following fractures.
More than half of men tend to have an identifiable and potentially secondary cause of osteoporosis. Therefore, it is mandatory to carefully evaluate all the possible causes and provide adequate treatment if available.
Treatment involves lifestyle changes, calcium and vitamin D supplementation if needed, treatment of secondary causes, and anti-osteoporosis therapy.
Currently approved treatments for males with osteoporosis include bisphosphonates (alendronate, risedronate, zoledronate), denosumab, teriparatide, and abaloparatide.
Romosozumab is not approved yet for males with osteoporosis in the United States.

Enhancing Healthcare Team Outcomes

Male patients with osteoporosis face a significantly higher risk of consecutive fractures and mortality following an initial fracture compared to women. Historically, osteoporosis was regarded primarily as a disease of postmenopausal females, leading to a lack of focus on men. Early identification of risk factors and the incorporation of screening into routine clinical practice are essential to reducing the morbidity and mortality associated with this condition. A comprehensive and proactive approach is vital to identifying at-risk patients, which includes taking detailed patient histories, assessing risk factors, reviewing medications, and staying updated on the latest local and global clinical guidelines.

Effective management of osteoporosis in men requires an interprofessional team, including rheumatologists, endocrinologists, primary care clinicians, nurse practitioners, dietitians, geriatricians, orthopedic surgeons, physical therapists, pharmacists, and radiologists. Each team member has a distinct role, but successful care relies on strategic coordination and clear communication among all participants, as well as with the patient. By leveraging the latest evidence and clinical guidelines, the team can deliver personalized, patient-centered care that maximizes treatment efficacy while minimizing adverse effects. This collaborative approach enhances patient outcomes, promotes safety, and prevents fractures, ensuring comprehensive and effective management of male osteoporosis.

References

[1]

Fuggle NR, Beaudart C, Bruyère O, Abrahamsen B, Al-Daghri N, Burlet N, Chandran M, Rosa MM, Cortet B, Demonceau C, Dere W, Halbout P, Hiligsmann M, Kanis JA, Kaufman JM, Kurth A, Lamy O, Laslop A, Maggi S, Matijevic R, McCloskey E, Mobasheri A, Prieto Yerro MC, Radermecker RP, Sabico S, Al-Saleh Y, Silverman S, Veronese N, Rizzoli R, Cooper C, Reginster JY, Harvey NC. Evidence-Based Guideline for the management of osteoporosis in men. Nature reviews. Rheumatology. 2024 Apr:20(4):241-251. doi: 10.1038/s41584-024-01094-9. Epub 2024 Mar 14 [PubMed PMID: 38485753]

Level 1 (high-level) evidence

[2]

Aibar-Almazán A, Voltes-Martínez A, Castellote-Caballero Y, Afanador-Restrepo DF, Carcelén-Fraile MDC, López-Ruiz E. Current Status of the Diagnosis and Management of Osteoporosis. International journal of molecular sciences. 2022 Aug 21:23(16):. doi: 10.3390/ijms23169465. Epub 2022 Aug 21 [PubMed PMID: 36012730]

[3]

Ramaraj K, Murugan PR, Amiya G, Govindaraj V, Vasudevan M, Thirumurugan M, Zhang Y, Abdullah SS, Thiyagarajan A. Emphatic information on bone mineral loss using quantitative ultrasound sonometer for expeditious prediction of osteoporosis. Scientific reports. 2023 Nov 8:13(1):19407. doi: 10.1038/s41598-023-44407-w. Epub 2023 Nov 8 [PubMed PMID: 37938240]

[4]

Towler DA. Commonalities Between Vasculature and Bone: An Osseocentric View of Arteriosclerosis. Circulation. 2017 Jan 24:135(4):320-322. doi: 10.1161/CIRCULATIONAHA.116.022562. Epub [PubMed PMID: 28115412]

[5]

Vescini F, Chiodini I, Falchetti A, Palermo A, Salcuni AS, Bonadonna S, De Geronimo V, Cesareo R, Giovanelli L, Brigo M, Bertoldo F, Scillitani A, Gennari L. Management of Osteoporosis in Men: A Narrative Review. International journal of molecular sciences. 2021 Dec 20:22(24):. doi: 10.3390/ijms222413640. Epub 2021 Dec 20 [PubMed PMID: 34948434]

Level 3 (low-level) evidence

[6]

Bandeira L, Silva BC, Bilezikian JP. Male osteoporosis. Archives of endocrinology and metabolism. 2022 Nov 11:66(5):739-747. doi: 10.20945/2359-3997000000563. Epub [PubMed PMID: 36382763]

[7]

Amarnath SS, Kumar V, Das SL. Classification of Osteoporosis. Indian journal of orthopaedics. 2023 Dec:57(Suppl 1):49-54. doi: 10.1007/s43465-023-01058-3. Epub 2023 Dec 6 [PubMed PMID: 38107823]

[8]

Björnsdottir S, Clarke BL, Mannstadt M, Langdahl BL. Male osteoporosis-what are the causes, diagnostic challenges, and management. Best practice & research. Clinical rheumatology. 2022 Sep:36(3):101766. doi: 10.1016/j.berh.2022.101766. Epub 2022 Aug 9 [PubMed PMID: 35961836]

[9]

Rinonapoli G, Ruggiero C, Meccariello L, Bisaccia M, Ceccarini P, Caraffa A. Osteoporosis in Men: A Review of an Underestimated Bone Condition. International journal of molecular sciences. 2021 Feb 20:22(4):. doi: 10.3390/ijms22042105. Epub 2021 Feb 20 [PubMed PMID: 33672656]

[10]

Gennari L, Bilezikian JP. New and developing pharmacotherapy for osteoporosis in men. Expert opinion on pharmacotherapy. 2018 Feb:19(3):253-264. doi: 10.1080/14656566.2018.1428559. Epub 2018 Jan 19 [PubMed PMID: 29350069]

Level 3 (low-level) evidence

[11]

Banu J. Causes, consequences, and treatment of osteoporosis in men. Drug design, development and therapy. 2013:7():849-60. doi: 10.2147/DDDT.S46101. Epub 2013 Aug 22 [PubMed PMID: 24009413]

[12]

Tomasiuk JM, Nowakowska-Płaza A, Wisłowska M, Głuszko P. Osteoporosis and diabetes - possible links and diagnostic difficulties. Reumatologia. 2023:61(4):294-304. doi: 10.5114/reum/170048. Epub 2023 Sep 3 [PubMed PMID: 37745139]

[13]

Alswat KA. Gender Disparities in Osteoporosis. Journal of clinical medicine research. 2017 May:9(5):382-387. doi: 10.14740/jocmr2970w. Epub 2017 Apr 1 [PubMed PMID: 28392857]

[14]

Khosla S, Amin S, Orwoll E. Osteoporosis in men. Endocrine reviews. 2008 Jun:29(4):441-64. doi: 10.1210/er.2008-0002. Epub 2008 May 1 [PubMed PMID: 18451258]

[15]

Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014 Nov:29(11):2520-6. doi: 10.1002/jbmr.2269. Epub [PubMed PMID: 24771492]

[16]

Ervin RB,Wright JD,Reed-Gillette D, Prevalence of leading types of dietary supplements used in the Third National Health and Nutrition Examination Survey, 1988--94. Advance data. 2004 Nov 9 [PubMed PMID: 15586828]

Level 3 (low-level) evidence

[17]

Sözen T, Özışık L, Başaran NÇ. An overview and management of osteoporosis. European journal of rheumatology. 2017 Mar:4(1):46-56. doi: 10.5152/eurjrheum.2016.048. Epub 2016 Dec 30 [PubMed PMID: 28293453]

Level 3 (low-level) evidence

[18]

Kannus P, Parkkari J, Sievänen H, Heinonen A, Vuori I, Järvinen M. Epidemiology of hip fractures. Bone. 1996 Jan:18(1 Suppl):57S-63S [PubMed PMID: 8717549]

[19]

Cauley JA, Cawthon PM, Peters KE, Cummings SR, Ensrud KE, Bauer DC, Taylor BC, Shikany JM, Hoffman AR, Lane NE, Kado DM, Stefanick ML, Orwoll ES, Osteoporotic Fractures in Men (MrOS) Study Research Group. Risk Factors for Hip Fracture in Older Men: The Osteoporotic Fractures in Men Study (MrOS). Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2016 Oct:31(10):1810-1819. doi: 10.1002/jbmr.2836. Epub 2016 Apr 8 [PubMed PMID: 26988112]

[20]

Matthis C, Weber U, O'Neill TW, Raspe H. Health impact associated with vertebral deformities: results from the European Vertebral Osteoporosis Study (EVOS). Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 1998:8(4):364-72 [PubMed PMID: 10024907]

[21]

European Prospective Osteoporosis Study (EPOS) Group, Felsenberg D, Silman AJ, Lunt M, Armbrecht G, Ismail AA, Finn JD, Cockerill WC, Banzer D, Benevolenskaya LI, Bhalla A, Bruges Armas J, Cannata JB, Cooper C, Dequeker J, Eastell R, Felsch B, Gowin W, Havelka S, Hoszowski K, Jajic I, Janott J, Johnell O, Kanis JA, Kragl G, Lopes Vaz A, Lorenc R, Lyritis G, Masaryk P, Matthis C, Miazgowski T, Parisi G, Pols HA, Poor G, Raspe HH, Reid DM, Reisinger W, Schedit-Nave C, Stepan JJ, Todd CJ, Weber K, Woolf AD, Yershova OB, Reeve J, O'Neill TW. Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS). Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2002 Apr:17(4):716-24 [PubMed PMID: 11918229]

[22]

Hasserius R, Karlsson MK, Nilsson BE, Redlund-Johnell I, Johnell O, European Vertebral Osteoporosis Study. Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: a 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2003 Jan:14(1):61-8 [PubMed PMID: 12577186]

[23]

Lips P. Epidemiology and predictors of fractures associated with osteoporosis. The American journal of medicine. 1997 Aug 18:103(2A):3S-8S; discussion 8S-11S [PubMed PMID: 9302892]

[24]

Mallmin H, Ljunghall S, Persson I, Naessén T, Krusemo UB, Bergström R. Fracture of the distal forearm as a forecaster of subsequent hip fracture: a population-based cohort study with 24 years of follow-up. Calcified tissue international. 1993 Apr:52(4):269-72 [PubMed PMID: 8467406]

[25]

Chalhoub D, Orwoll ES, Cawthon PM, Ensrud KE, Boudreau R, Greenspan S, Newman AB, Zmuda J, Bauer D, Cummings S, Cauley JA, Osteoporotic Fractures in Men (MrOS) Study Research Group. Areal and volumetric bone mineral density and risk of multiple types of fracture in older men. Bone. 2016 Nov:92():100-106. doi: 10.1016/j.bone.2016.08.014. Epub 2016 Aug 20 [PubMed PMID: 27554426]

[26]

Bonjour JP, Theintz G, Law F, Slosman D, Rizzoli R. Peak bone mass. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 1994:4 Suppl 1():7-13 [PubMed PMID: 8081064]

[27]

Trotter M, Hixon BB. Sequential changes in weight, density, and percentage ash weight of human skeletons from an early fetal period through old age. The Anatomical record. 1974 May:179(1):1-18 [PubMed PMID: 4821360]

[28]

Gilsanz V, Gibbens DT, Roe TF, Carlson M, Senac MO, Boechat MI, Huang HK, Schulz EE, Libanati CR, Cann CC. Vertebral bone density in children: effect of puberty. Radiology. 1988 Mar:166(3):847-50 [PubMed PMID: 3340782]

[29]

Seeman E. From density to structure: growing up and growing old on the surfaces of bone. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 1997 Apr:12(4):509-21 [PubMed PMID: 9101362]

[30]

Seeman E. Pathogenesis of bone fragility in women and men. Lancet (London, England). 2002 May 25:359(9320):1841-50 [PubMed PMID: 12044392]

[31]

Chevalley T, Rizzoli R. Acquisition of peak bone mass. Best practice & research. Clinical endocrinology & metabolism. 2022 Mar:36(2):101616. doi: 10.1016/j.beem.2022.101616. Epub 2022 Jan 20 [PubMed PMID: 35125324]

[32]

Herrera A, Lobo-Escolar A, Mateo J, Gil J, Ibarz E, Gracia L. Male osteoporosis: A review. World journal of orthopedics. 2012 Dec 18:3(12):223-34. doi: 10.5312/wjo.v3.i12.223. Epub [PubMed PMID: 23362466]

[33]

Finkelstein JS, Klibanski A, Neer RM, Greenspan SL, Rosenthal DI, Crowley WF Jr. Osteoporosis in men with idiopathic hypogonadotropic hypogonadism. Annals of internal medicine. 1987 Mar:106(3):354-61 [PubMed PMID: 3544993]

[34]

Guo CY, Jones TH, Eastell R. Treatment of isolated hypogonadotropic hypogonadism effect on bone mineral density and bone turnover. The Journal of clinical endocrinology and metabolism. 1997 Feb:82(2):658-65 [PubMed PMID: 9024272]

[35]

Manolagas SC, O'Brien CA, Almeida M. The role of estrogen and androgen receptors in bone health and disease. Nature reviews. Endocrinology. 2013 Dec:9(12):699-712. doi: 10.1038/nrendo.2013.179. Epub 2013 Sep 17 [PubMed PMID: 24042328]

[36]

Vanderschueren D, Vandenput L, Boonen S, Lindberg MK, Bouillon R, Ohlsson C. Androgens and bone. Endocrine reviews. 2004 Jun:25(3):389-425 [PubMed PMID: 15180950]

[37]

Hunter DJ, Sambrook PN. Bone loss. Epidemiology of bone loss. Arthritis research. 2000:2(6):441-5 [PubMed PMID: 11094456]

[38]

Jones G, Nguyen T, Sambrook P, Kelly PJ, Eisman JA. Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study. BMJ (Clinical research ed.). 1994 Sep 17:309(6956):691-5 [PubMed PMID: 7950520]

[39]

Hannan MT, Felson DT, Dawson-Hughes B, Tucker KL, Cupples LA, Wilson PW, Kiel DP. Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2000 Apr:15(4):710-20 [PubMed PMID: 10780863]

[40]

Nieves JW, Formica C, Ruffing J, Zion M, Garrett P, Lindsay R, Cosman F. Males have larger skeletal size and bone mass than females, despite comparable body size. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2005 Mar:20(3):529-35 [PubMed PMID: 15746999]

[41]

Fink HA, Ewing SK, Ensrud KE, Barrett-Connor E, Taylor BC, Cauley JA, Orwoll ES. Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. The Journal of clinical endocrinology and metabolism. 2006 Oct:91(10):3908-15 [PubMed PMID: 16849417]

[42]

Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, Adler RA. Osteoporosis in Men. Endotext. 2000:(): [PubMed PMID: 32515917]

[43]

Cawthon PM, Shahnazari M, Orwoll ES, Lane NE. Osteoporosis in men: findings from the Osteoporotic Fractures in Men Study (MrOS). Therapeutic advances in musculoskeletal disease. 2016 Feb:8(1):15-27. doi: 10.1177/1759720X15621227. Epub [PubMed PMID: 26834847]

Level 3 (low-level) evidence

[44]

Finkelstein JS, Lee H, Leder BZ, Burnett-Bowie SA, Goldstein DW, Hahn CW, Hirsch SC, Linker A, Perros N, Servais AB, Taylor AP, Webb ML, Youngner JM, Yu EW. Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. The Journal of clinical investigation. 2016 Mar 1:126(3):1114-25. doi: 10.1172/JCI84137. Epub 2016 Feb 22 [PubMed PMID: 26901812]

[45]

Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I. Estradiol in elderly men. The aging male : the official journal of the International Society for the Study of the Aging Male. 2002 Jun:5(2):98-102 [PubMed PMID: 12198740]

[46]

Smith MR. Androgen deprivation therapy for prostate cancer: new concepts and concerns. Current opinion in endocrinology, diabetes, and obesity. 2007 Jun:14(3):247-54 [PubMed PMID: 17940447]

Level 3 (low-level) evidence

[47]

Verschueren S, Gielen E, O'Neill TW, Pye SR, Adams JE, Ward KA, Wu FC, Szulc P, Laurent M, Claessens F, Vanderschueren D, Boonen S. Sarcopenia and its relationship with bone mineral density in middle-aged and elderly European men. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2013 Jan:24(1):87-98. doi: 10.1007/s00198-012-2057-z. Epub 2012 Jul 10 [PubMed PMID: 22776861]

Level 2 (mid-level) evidence

[48]

Marcu F, Bogdan F, Muţiu G, Lazăr L. The histopathological study of osteoporosis. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2011:52(1 Suppl):321-5 [PubMed PMID: 21424070]

[49]

Ganesan K, Jandu JS, Anastasopoulou C, Ahsun S, Roane D. Secondary Osteoporosis. StatPearls. 2025 Jan:(): [PubMed PMID: 29262237]

[50]

Watts NB, Adler RA, Bilezikian JP, Drake MT, Eastell R, Orwoll ES, Finkelstein JS, Endocrine Society. Osteoporosis in men: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism. 2012 Jun:97(6):1802-22. doi: 10.1210/jc.2011-3045. Epub [PubMed PMID: 22675062]

Level 1 (high-level) evidence

[51]

Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R, National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2014 Oct:25(10):2359-81. doi: 10.1007/s00198-014-2794-2. Epub 2014 Aug 15 [PubMed PMID: 25182228]

Level 1 (high-level) evidence

[52]

Cheng N, Green ME. Osteoporosis screening for men: are family physicians following the guidelines? Canadian family physician Medecin de famille canadien. 2008 Aug:54(8):1140-1141, 1141.e1-5 [PubMed PMID: 18697977]

[53]

US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Kubik M, Landefeld CS, Mangione CM, Phipps MG, Pignone M, Silverstein M, Simon MA, Tseng CW, Wong JB. Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Jun 26:319(24):2521-2531. doi: 10.1001/jama.2018.7498. Epub [PubMed PMID: 29946735]

[54]

Tenne M, McGuigan F, Besjakov J, Gerdhem P, Åkesson K. Degenerative changes at the lumbar spine--implications for bone mineral density measurement in elderly women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2013 Apr:24(4):1419-28. doi: 10.1007/s00198-012-2048-0. Epub 2012 Jun 26 [PubMed PMID: 22733092]

[55]

Livshits G, Ermakov S, Popham M, Macgregor AJ, Sambrook PN, Spector TD, Williams FM. Evidence that bone mineral density plays a role in degenerative disc disease: the UK Twin Spine study. Annals of the rheumatic diseases. 2010 Dec:69(12):2102-6. doi: 10.1136/ard.2010.131441. Epub 2010 Jun 22 [PubMed PMID: 20570838]

[56]

Krueger D, Tanner SB, Szalat A, Malabanan A, Prout T, Lau A, Rosen HN, Shuhart C. DXA Reporting Updates: 2023 Official Positions of the International Society for Clinical Densitometry. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2024 Jan-Mar:27(1):101437. doi: 10.1016/j.jocd.2023.101437. Epub 2023 Nov 2 [PubMed PMID: 38011777]

[57]

Métrailler A, Hans D, Lamy O, Gonzalez Rodriguez E, Shevroja E. Heel quantitative ultrasound (QUS) predicts incident fractures independently of trabecular bone score (TBS), bone mineral density (BMD), and FRAX: the OsteoLaus Study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2023 Aug:34(8):1401-1409. doi: 10.1007/s00198-023-06728-4. Epub 2023 May 8 [PubMed PMID: 37154943]

[58]

Boehm E, Kraft E, Biebl JT, Wegener B, Stahl R, Feist-Pagenstert I. Quantitative computed tomography has higher sensitivity detecting critical bone mineral density compared to dual-energy X-ray absorptiometry in postmenopausal women and elderly men with osteoporotic fractures: a real-life study. Archives of orthopaedic and trauma surgery. 2024 Jan:144(1):179-188. doi: 10.1007/s00402-023-05070-y. Epub 2023 Oct 5 [PubMed PMID: 37796283]

[59]

Walsh N, Barr O, Lang D, Currid M, Hoey C. Peripheral bone density measurement: An interdisciplinary initiative for improving health outcomes for people with learning disabilities. Journal of intellectual disabilities : JOID. 2022 Mar:26(1):18-28. doi: 10.1177/1744629520950136. Epub 2020 Aug 20 [PubMed PMID: 32815754]

[60]

Palomo T, Muszkat P, Weiler FG, Dreyer P, Brandão CMA, Silva BC. Update on trabecular bone score. Archives of endocrinology and metabolism. 2022 Nov 11:66(5):694-706. doi: 10.20945/2359-3997000000559. Epub [PubMed PMID: 36382759]

[61]

Lems WF, Paccou J, Zhang J, Fuggle NR, Chandran M, Harvey NC, Cooper C, Javaid K, Ferrari S, Akesson KE, International Osteoporosis Foundation Fracture Working Group. Vertebral fracture: epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2021 Mar:32(3):399-411. doi: 10.1007/s00198-020-05804-3. Epub 2021 Jan 21 [PubMed PMID: 33475820]

[62]

Heilmeier U, Youm J, Torabi S, Link TM. Osteoporosis Imaging in the Geriatric Patient. Current radiology reports. 2016 Apr:4(4):. pii: 18. Epub 2016 Feb 15 [PubMed PMID: 27482472]

[63]

Xu Y, Bao Y, Wang M, Wu Q. Smoking and fracture risk in men: a meta-analysis of cohort studies, using both frequentist and Bayesian approaches. Scientific reports. 2022 Jun 3:12(1):9270. doi: 10.1038/s41598-022-13356-1. Epub 2022 Jun 3 [PubMed PMID: 35661791]

Level 1 (high-level) evidence

[64]

Ward KD, Klesges RC. A meta-analysis of the effects of cigarette smoking on bone mineral density. Calcified tissue international. 2001 May:68(5):259-70 [PubMed PMID: 11683532]

Level 1 (high-level) evidence

[65]

Savikangas T, Suominen TH, Alén M, Rantalainen T, Sipilä S. Changes in femoral neck bone mineral density and structural strength during a 12-month multicomponent exercise intervention among older adults - Does accelerometer-measured physical activity matter? Bone. 2024 Jan:178():116951. doi: 10.1016/j.bone.2023.116951. Epub 2023 Oct 31 [PubMed PMID: 37913888]

[66]

Cao Y, Hu Y, Lei F, Zhang X, Liu W, Huang X, Sun T, Lin L, Yi M, Li Y, Zhang J, Li Y, Wang G, Cheng Z. Associations between leisure-time physical activity and the prevalence and incidence of osteoporosis disease: Cross-sectional and prospective findings from the UK biobank. Bone. 2024 Oct:187():117208. doi: 10.1016/j.bone.2024.117208. Epub 2024 Jul 22 [PubMed PMID: 39047901]

Level 2 (mid-level) evidence

[67]

Kanis JA, Johansson H, Johnell O, Oden A, De Laet C, Eisman JA, Pols H, Tenenhouse A. Alcohol intake as a risk factor for fracture. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2005 Jul:16(7):737-42 [PubMed PMID: 15455194]

[68]

DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ (Clinical research ed.). 2010 Jan 12:340():b5463. doi: 10.1136/bmj.b5463. Epub 2010 Jan 12 [PubMed PMID: 20068257]

Level 1 (high-level) evidence

[69]

Xiao Q, Murphy RA, Houston DK, Harris TB, Chow WH, Park Y. Dietary and supplemental calcium intake and cardiovascular disease mortality: the National Institutes of Health-AARP diet and health study. JAMA internal medicine. 2013 Apr 22:173(8):639-46. doi: 10.1001/jamainternmed.2013.3283. Epub [PubMed PMID: 23381719]

Level 3 (low-level) evidence

[70]

Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clinic proceedings. 2008 Sep:83(9):1032-45. doi: 10.4065/83.9.1032. Epub [PubMed PMID: 18775204]

[71]

LeBoff MS, Greenspan SL, Insogna KL, Lewiecki EM, Saag KG, Singer AJ, Siris ES. The clinician's guide to prevention and treatment of osteoporosis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2022 Oct:33(10):2049-2102. doi: 10.1007/s00198-021-05900-y. Epub 2022 Apr 28 [PubMed PMID: 35478046]

[72]

Hildebrand GK,Kasi A, Denosumab. StatPearls. 2022 Jan; [PubMed PMID: 30571009]

[73]

Langdahl BL, Teglbjærg CS, Ho PR, Chapurlat R, Czerwinski E, Kendler DL, Reginster JY, Kivitz A, Lewiecki EM, Miller PD, Bolognese MA, McClung MR, Bone HG, Ljunggren Ö, Abrahamsen B, Gruntmanis U, Yang YC, Wagman RB, Mirza F, Siddhanti S, Orwoll E. A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial. The Journal of clinical endocrinology and metabolism. 2015 Apr:100(4):1335-42. doi: 10.1210/jc.2014-4079. Epub 2015 Jan 21 [PubMed PMID: 25607608]

[74]

Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, Leder BZ, Goessl C, Denosumab HALT Prostate Cancer Study Group. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. The New England journal of medicine. 2009 Aug 20:361(8):745-55. doi: 10.1056/NEJMoa0809003. Epub 2009 Aug 11 [PubMed PMID: 19671656]

[75]

Yanbeiy ZA, Hansen KE. Denosumab in the treatment of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis. Drug design, development and therapy. 2019:13():2843-2852. doi: 10.2147/DDDT.S148654. Epub 2019 Aug 14 [PubMed PMID: 31616133]

Level 1 (high-level) evidence

[76]

Kendler D, Chines A, Clark P, Ebeling PR, McClung M, Rhee Y, Huang S, Stad RK. Bone Mineral Density After Transitioning From Denosumab to Alendronate. The Journal of clinical endocrinology and metabolism. 2020 Mar 1:105(3):e255-64. doi: 10.1210/clinem/dgz095. Epub [PubMed PMID: 31665314]

[77]

Fernández-Carneado J, Vallès-Miret M, Arrastia-Casado S, Almazán-Moga A, Macias MJ, Martin-Malpartida P, Vilaseca M, Díaz-Lobo M, Vazquez M, Sanahuja RM, Gambús G, Ponsati B. First Generic Teriparatide: Structural and Biological Sameness to Its Reference Medicinal Product. Pharmaceutics. 2024 Apr 13:16(4):. doi: 10.3390/pharmaceutics16040537. Epub 2024 Apr 13 [PubMed PMID: 38675198]

[78]

Tabacco G, Bilezikian JP. Osteoanabolic and dual action drugs. British journal of clinical pharmacology. 2019 Jun:85(6):1084-1094. doi: 10.1111/bcp.13766. Epub 2019 Apr 3 [PubMed PMID: 30218587]

[79]

Eastell R, Walsh JS. Anabolic treatment for osteoporosis: teriparatide. Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases. 2017 May-Aug:14(2):173-178. doi: 10.11138/ccmbm/2017.14.1.173. Epub 2017 Oct 25 [PubMed PMID: 29263728]

Level 3 (low-level) evidence

[80]

Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. The New England journal of medicine. 2001 May 10:344(19):1434-41 [PubMed PMID: 11346808]

Level 1 (high-level) evidence

[81]

Kaufman JM, Orwoll E, Goemaere S, San Martin J, Hossain A, Dalsky GP, Lindsay R, Mitlak BH. Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2005 May:16(5):510-6 [PubMed PMID: 15322742]

Level 1 (high-level) evidence

[82]

Miller PD, Lewiecki EM, Krohn K, Schwartz E. Teriparatide: Label changes and identifying patients for long-term use. Cleveland Clinic journal of medicine. 2021 Sep 1:88(9):489-493. doi: 10.3949/ccjm.88a.21011. Epub 2021 Sep 1 [PubMed PMID: 34470753]

[83]

Ayalon-Dangur I, Rudman Y, Tsvetov G, Slutzky-Shraga I, Akirov A, Shimon I, Hirsch D, Gorshtein A. Long-term effectiveness of zoledronic acid in patients with Paget's disease of bone - a retrospective cohort study. Endocrine. 2024 Aug:85(2):873-882. doi: 10.1007/s12020-024-03791-7. Epub 2024 Mar 30 [PubMed PMID: 38555314]

Level 2 (mid-level) evidence

[84]

Hattersley G, Dean T, Corbin BA, Bahar H, Gardella TJ. Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. Endocrinology. 2016 Jan:157(1):141-9. doi: 10.1210/en.2015-1726. Epub 2015 Nov 12 [PubMed PMID: 26562265]

[85]

Tella SH, Kommalapati A, Correa R. Profile of Abaloparatide and Its Potential in the Treatment of Postmenopausal Osteoporosis. Cureus. 2017 May 31:9(5):e1300. doi: 10.7759/cureus.1300. Epub 2017 May 31 [PubMed PMID: 28680788]

[86]

Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, Alexandersen P, Zerbini CA, Hu MY, Harris AG, Fitzpatrick LA, Cosman F, Christiansen C, ACTIVE Study Investigators. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016 Aug 16:316(7):722-33. doi: 10.1001/jama.2016.11136. Epub [PubMed PMID: 27533157]

Level 3 (low-level) evidence

[87]

Dhaliwal R, Kendler D, Saag K, Ing SW, Singer A, Adler RA, Pearman L, Wang Y, Mitlak B. Response rates for lumbar spine, total hip, and femoral neck bone mineral density in men treated with abaloparatide: results from the ATOM study. JBMR plus. 2024 Feb:8(2):ziae009. doi: 10.1093/jbmrpl/ziae009. Epub 2024 Jan 27 [PubMed PMID: 38505522]

[88]

Matsumoto T, Sone T, Soen S, Tanaka S, Yamashita A, Inoue T. Abaloparatide Increases Lumbar Spine and Hip BMD in Japanese Patients With Osteoporosis: The Phase 3 ACTIVE-J Study. The Journal of clinical endocrinology and metabolism. 2022 Sep 28:107(10):e4222-e4231. doi: 10.1210/clinem/dgac486. Epub [PubMed PMID: 35977548]

[89]

Davenport C, Gravel P, Wang Y, Williams SA, Wieland A, Mitlak B. Real-World Evidence to Support the Registration of a New Osteoporosis Medicinal Product in Europe. Therapeutic innovation & regulatory science. 2024 May:58(3):505-518. doi: 10.1007/s43441-024-00616-7. Epub 2024 Feb 10 [PubMed PMID: 38341388]

[90]

Merlotti D, Falchetti A, Chiodini I, Gennari L. Efficacy and safety of abaloparatide for the treatment of post-menopausal osteoporosis. Expert opinion on pharmacotherapy. 2019 May:20(7):805-811. doi: 10.1080/14656566.2019.1583208. Epub 2019 Mar 11 [PubMed PMID: 30856013]

Level 3 (low-level) evidence

[91]

Lim SY, Bolster MB. Profile of romosozumab and its potential in the management of osteoporosis. Drug design, development and therapy. 2017:11():1221-1231. doi: 10.2147/DDDT.S127568. Epub 2017 Apr 13 [PubMed PMID: 28458516]

[92]

Di Monaco M, Castiglioni C, Bardesono F. Letter to the editor: consideration on: 'What is the risk of cardiovascular events in osteoporotic patients treated with romosozumab?' by Reid I.R. Expert opinion on drug safety. 2023 Jan:22(1):103-104. doi: 10.1080/14740338.2023.2173737. Epub 2023 Jan 29 [PubMed PMID: 36710441]

Level 3 (low-level) evidence

[93]

Kerschan-Schindl K, Romosozumab: a novel bone anabolic treatment option for osteoporosis? Wiener medizinische Wochenschrift (1946). 2019 Dec 19; [PubMed PMID: 31858345]

[94]

. Romosozumab for osteoporosis. Australian prescriber. 2021 Jun:44(3):109-110. doi: 10.18773/austprescr.2021.021. Epub 2021 Apr 20 [PubMed PMID: 34211250]

[95]

Grech A, Breck J, Heidelbaugh J. Adverse effects of testosterone replacement therapy: an update on the evidence and controversy. Therapeutic advances in drug safety. 2014 Oct:5(5):190-200. doi: 10.1177/2042098614548680. Epub [PubMed PMID: 25360240]

Level 3 (low-level) evidence

[96]

Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, Cunningham GR, Granger CB, Khera M, Thompson IM Jr, Wang Q, Wolski K, Davey D, Kalahasti V, Khan N, Miller MG, Snabes MC, Chan A, Dubcenco E, Li X, Yi T, Huang B, Pencina KM, Travison TG, Nissen SE, TRAVERSE Study Investigators. Cardiovascular Safety of Testosterone-Replacement Therapy. The New England journal of medicine. 2023 Jul 13:389(2):107-117. doi: 10.1056/NEJMoa2215025. Epub 2023 Jun 16 [PubMed PMID: 37326322]

[97]

Grossmann M, Anawalt BD, Yeap BB. Testosterone therapy in older men: clinical implications of recent landmark trials. European journal of endocrinology. 2024 Jul 2:191(1):R22-R31. doi: 10.1093/ejendo/lvae071. Epub [PubMed PMID: 38917356]

[98]

Nayak S, Greenspan SL. Osteoporosis Treatment Efficacy for Men: A Systematic Review and Meta-Analysis. Journal of the American Geriatrics Society. 2017 Mar:65(3):490-495. doi: 10.1111/jgs.14668. Epub 2016 Nov 7 [PubMed PMID: 28304090]

Level 1 (high-level) evidence

[99]

Curtis EM, Cooper C, Harvey NC. Cardiovascular safety of calcium, magnesium and strontium: what does the evidence say? Aging clinical and experimental research. 2021 Mar:33(3):479-494. doi: 10.1007/s40520-021-01799-x. Epub 2021 Feb 9 [PubMed PMID: 33565045]

[100]

Kaufman JM, Audran M, Bianchi G, Braga V, Diaz-Curiel M, Francis RM, Goemaere S, Josse R, Palacios S, Ringe JD, Felsenberg D, Boonen S. Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men. The Journal of clinical endocrinology and metabolism. 2013 Feb:98(2):592-601. doi: 10.1210/jc.2012-3048. Epub 2013 Jan 22 [PubMed PMID: 23341486]

[101]

Cosman F. Anabolic Therapy and Optimal Treatment Sequences for Patients With Osteoporosis at High Risk for Fracture. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2020 Jul:26(7):777-786. doi: 10.4158/EP-2019-0596. Epub 2020 Nov 24 [PubMed PMID: 33471647]

[102]

Leder BZ, Neer RM, Wyland JJ, Lee HW, Burnett-Bowie SM, Finkelstein JS. Effects of teriparatide treatment and discontinuation in postmenopausal women and eugonadal men with osteoporosis. The Journal of clinical endocrinology and metabolism. 2009 Aug:94(8):2915-21. doi: 10.1210/jc.2008-2630. Epub 2009 May 12 [PubMed PMID: 19435827]

[103]

Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR, FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27:296(24):2927-38 [PubMed PMID: 17190893]

Level 1 (high-level) evidence

[104]

Diab DL, Watts NB. Bisphosphonate drug holiday: who, when and how long. Therapeutic advances in musculoskeletal disease. 2013 Jun:5(3):107-11. doi: 10.1177/1759720X13477714. Epub [PubMed PMID: 23858334]

Level 3 (low-level) evidence

[105]

Villa JC, Gianakos A, Lane JM. Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday. HSS journal : the musculoskeletal journal of Hospital for Special Surgery. 2016 Feb:12(1):66-73. doi: 10.1007/s11420-015-9469-1. Epub 2015 Dec 9 [PubMed PMID: 26855630]

[106]

Williams C, Anastasopoulou C, Sapra A. Biochemical Markers of Osteoporosis. StatPearls. 2025 Jan:(): [PubMed PMID: 32644732]

[107]

Cawthon PM. Gender differences in osteoporosis and fractures. Clinical orthopaedics and related research. 2011 Jul:469(7):1900-5. doi: 10.1007/s11999-011-1780-7. Epub [PubMed PMID: 21264553]

[108]

Kannegaard PN, van der Mark S, Eiken P, Abrahamsen B. Excess mortality in men compared with women following a hip fracture. National analysis of comedications, comorbidity and survival. Age and ageing. 2010 Mar:39(2):203-9. doi: 10.1093/ageing/afp221. Epub 2010 Jan 14 [PubMed PMID: 20075035]

[109]

Pande I, Scott DL, O'Neill TW, Pritchard C, Woolf AD, Davis MJ. Quality of life, morbidity, and mortality after low trauma hip fracture in men. Annals of the rheumatic diseases. 2006 Jan:65(1):87-92 [PubMed PMID: 16079173]

Level 2 (mid-level) evidence