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Treatment of osteoporosis in men

Treatment of osteoporosis in men
Literature review current through: Jan 2024.
This topic last updated: Aug 23, 2023.

INTRODUCTION — Osteoporosis is a leading cause of morbidity and mortality in older people. While less common in men than women, the mortality rate associated with hip fractures [1,2], as well as vertebral and other major fractures [3], is higher in men than in women; in part, this is related to older age and a greater number of comorbid conditions at the time of fracture. In addition, men are even less likely than women to be evaluated or receive antiresorptive therapy after a hip fracture (4.5 versus 49.5 percent, respectively) [4-6].

The treatment of osteoporosis in men consists of lifestyle measures, hormonal therapy (when indicated), and/or drug therapy. An overview of the approach to therapy of osteoporosis in men will be presented here. The diagnosis, evaluation, and epidemiology of osteoporosis in men are discussed separately. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men" and "Etiology of osteoporosis in men".)

LIFESTYLE MEASURES — In general, lifestyle modifications should be encouraged for all men with osteoporosis. A weight-bearing exercise regimen may be modestly beneficial, given the association of reduced physical activity with bone loss and fracture in older men and the positive effect of exercise in women with osteoporosis (see "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Exercise' and "Etiology of osteoporosis in men", section on 'Lifestyle factors'). In addition, smoking and excessive alcohol intake should be avoided.

The Recommended Daily Allowance for total calcium intake (from diet and supplements) in men is 1000 mg per day for men aged 19 to 70 years and 1200 mg per day for men aged 71 years and older. The Recommended Daily Allowance for vitamin D is 600 international units (15 mcg) per day for men aged 19 to 70 years and 800 international units (20 mcg) per day for men aged 71 years and older. Older persons confined indoors and other high-risk groups may have low serum 25-hydroxyvitamin D (25[OH]D) concentrations at this intake level and may require higher intakes of vitamin D. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Groups at high risk'.)

In some trials, vitamin D has been shown to reduce fracture risk in adults when administered at a dose of at least 700 international units/day and when given with calcium supplements (see "Calcium and vitamin D supplementation in osteoporosis"). However, in most cases, the addition of pharmacologic therapy is necessary for the treatment of osteoporosis in men [7].

MANAGEMENT OF UNDERLYING CONDITIONS — If osteoporosis is due to another condition (eg, hypogonadism, gastrointestinal disease, hypercalciuria), the underlying cause should be treated and potential offending agents (eg, glucocorticoids, alcohol, tobacco) should be eliminated whenever possible. Many conditions may contribute to osteoporosis in men (table 1). Some of the more common underlying causes are reviewed below. (See "Etiology of osteoporosis in men".)

Hypogonadism — For hypogonadal men who have a high risk for fracture, we suggest the addition of osteoporosis pharmacotherapy to testosterone therapy. (See 'Patient selection' below and 'Choice of therapy' below.)

The impact of hypogonadism on bone mineral density (BMD) and fracture risk in men is reviewed separately, as are the diagnosis and treatment of male hypogonadism. (See "Etiology of osteoporosis in men", section on 'Hypogonadism' and "Clinical features and diagnosis of male hypogonadism" and "Testosterone treatment of male hypogonadism".)

Testosterone therapy has skeletal benefits in men with serum testosterone levels below the normal range, as illustrated by the studies described below.

Congenital hypogonadism — Severe hypogonadism (serum testosterone levels in the prepubertal range) is seen in men with idiopathic hypogonadotropic hypogonadism (IHH) [8] and in some men with Klinefelter syndrome or other congenital disorders. In men with IHH, BMD is low and increases modestly with androgen replacement [9]. Androgen replacement leads to greater increases in BMD if initiated before skeletal maturity [9,10]. Nonetheless, in men with congenital forms of hypogonadism, BMD remains substantially lower than in eugonadal, healthy men despite prolonged testosterone replacement.

Acquired hypogonadism

Hypogonadism due to an underlying disorder – Severe acquired hypogonadism is uncommon but can occur in men with pituitary tumors or testicular damage. In men with acquired hypogonadism due to an identifiable organic disorder, BMD is reduced and increases modestly with testosterone therapy (eg, 5 percent by spine dual-energy x-ray absorptiometry [DXA] and 14 percent by quantitative computed tomography [QCT] in one report) [11]. The response to testosterone administration is greatest in previously untreated men with the lowest BMD at baseline [10].

Functional hypogonadism – In men with functional hypogonadism (ie, age-related declines in testosterone, or "low T" syndrome), the effects of testosterone administration on fracture risk remain uncertain. Given this uncertainty, we agree with the recommendation from the Endocrine Society to add a pharmacologic agent with proven antifracture efficacy (eg, a bisphosphonate or teriparatide) in testosterone-treated hypogonadal men with high risk of fracture [12]. (See 'Patient selection' below and 'Choice of therapy' below.)

Only a few trials have examined the skeletal effects of testosterone in older men with low serum testosterone levels due to functional hypogonadism. Two small trials (n = 70 and n = 48) in men aged ≥60 or 65 years with testosterone levels below the reference range reported improvement in spine BMD by DXA with testosterone supplementation [13,14]. However, in another trial of 108 men, changes in BMD were similar in men treated with testosterone or placebo, probably because the mean baseline testosterone concentration (367 ng/dL [12.7 nmol/L]) was too high to demonstrate a beneficial effect on BMD [15].

In the Testosterone Trials, men aged ≥65 years (n = 211) with baseline serum testosterone level <275 ng/dL (9.5 nmol/L) were randomly assigned to treatment with testosterone or placebo. After 12 months, testosterone therapy led to a greater increase in mean lumbar spine trabecular volumetric BMD (7.5 versus 0.8 percent) (figure 1), as well as greater increases in lumbar peripheral volumetric BMD (as measured by QCT) and hip trabecular and peripheral volumetric BMD [16]. To a lesser degree, testosterone also increased areal BMD of the lumbar spine by DXA. (See "Approach to older males with low testosterone".)

In one physiologic study, declines in BMD due to gonadal steroid deficiency generally did not occur until testosterone levels approached 200 ng/dL (6.9 nmol/L) or below [17]. Thus, the relatively modest increase in BMD with testosterone administration in the Testosterone Trials is perhaps not surprising given that the average baseline testosterone level was 230 ng/dL (8 nmol/L). Of note, none of the published testosterone trials has evaluated the impact of testosterone on fracture risk, although the TRAVERSE trial may provide data about this important outcome [18].

Glucocorticoid-induced osteoporosis — Glucocorticoid therapy is associated with an appreciable risk of bone loss, which is most pronounced in the first few months of use. In addition, glucocorticoids increase fracture risk, and fractures occur at higher BMD values than those associated with fracture in postmenopausal osteoporosis. The increased risk of fracture has been reported with doses of prednisone or its equivalent as low as 2.5 to 7.5 mg daily. (See "Clinical features and evaluation of glucocorticoid-induced osteoporosis", section on 'Epidemiology and risk factors'.)

Glucocorticoid-induced bone loss should be treated aggressively, particularly in individuals at high risk for fracture (eg, prior fragility fracture, high-dose glucocorticoids, frequent falls). In other individuals, clinical risk factor and BMD assessment may help guide therapy. The prevention and treatment of glucocorticoid-induced bone loss in adults is reviewed in detail separately. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)

Androgen deprivation therapy — Androgen deprivation therapy (bilateral orchiectomy or gonadotropin-releasing hormone [GnRH] agonist administration) reduces BMD in men with prostate cancer and increases the risk of clinical fractures. The management of osteoporosis in men treated with androgen deprivation therapy is reviewed in detail separately. (See "Side effects of androgen deprivation therapy", section on 'Osteoporosis and bone fractures'.)

Gastrointestinal disorders — Osteoporosis is common in patients with malabsorptive disorders (eg, celiac disease) and in those with inflammatory bowel diseases (eg, Crohn disease, ulcerative colitis). In patients with celiac disease, osteoporosis is due, in part, to secondary hyperparathyroidism related to vitamin D deficiency. In patients with severely low vitamin D levels (and particularly if the serum parathyroid hormone [PTH] is high), the need for osteoporosis therapy should be re-evaluated after vitamin D repletion. In patients with severe vitamin D deficiency, osteomalacia may be present, and BMD may increase markedly with vitamin D and calcium administration alone. (See "Clinical manifestations, diagnosis, and treatment of osteomalacia in adults", section on 'Treatment' and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Vitamin D replacement'.)

Similarly, treatment of celiac disease with a gluten-free diet may be sufficient for a significant improvement in BMD. (See "Management of celiac disease in adults", section on 'Dietary counseling'.)

Patients with inflammatory bowel disease have multiple potential causes of osteoporosis, including disease-related inflammatory activity, glucocorticoid therapy, hypogonadism, and nutritional deficiencies. The treatment of osteoporosis in patients with inflammatory bowel disease is reviewed separately. (See "Metabolic bone disease in inflammatory bowel disease".)

Hypercalciuria — BMD is frequently reduced in men with hypercalciuria. Reduced BMD is most often observed in men who have fasting hypercalciuria and PTH levels in the lower end of the normal range, suggesting that urinary calcium is increased because of excessive bone resorption rather than increased calcium absorption or a primary renal calcium leak. For these men, a low-calcium diet should be avoided as it may further exacerbate BMD losses. (See 'Lifestyle measures' above.)

OSTEOPOROSIS PHARMACOTHERAPY

Patient selection — Men with the highest risk of fracture are the ones most likely to benefit from osteoporosis drug therapy; therefore, patient selection should be based upon fracture risk, as determined by a combination of bone mineral density (BMD) and clinical risk factors. The following approach is largely in agreement with guidelines from the Bone Health and Osteoporosis Foundation (BHOF, previously the National Osteoporosis Foundation [NOF]) and the Endocrine Society (table 2) [12,19]. Additional guidelines have been published for the treatment of osteoporosis in men. Although these guidelines are useful, osteoporosis treatment should remain individualized through shared decision-making between patient and clinician. (See 'Society guideline links' below.)

For men with osteoporosis (history of fragility fracture, or a T-score below -2.5 in men aged ≥50 years), we recommend osteoporosis pharmacotherapy. This recommendation is widely accepted, though largely based on the proven efficacy of pharmacologic therapy in women with osteoporosis. (See 'Choice of therapy' below and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men", section on 'Diagnosis of osteoporosis'.)

For testosterone-treated hypogonadal men who have a high risk for fracture, we suggest the addition of osteoporosis pharmacotherapy to testosterone therapy. In the absence of definitive data upon which to objectively classify fracture risk in hypogonadal men, we consider high risk to include the following:

High-dose glucocorticoids

Frequent falls

Recent fragility fracture, particularly with a BMD T-score ≤-2.5 at any skeletal site

BMD T-score ≤-3.0

BMD T-score ≤-2.5 after adequate testosterone replacement therapy for ≥2 years (based upon clinical trial data in men showing that testosterone continues to improve BMD for at least two years [13])

For men aged ≥50 years with T-scores between -1.0 and -2.5 who are at high risk for fracture, we suggest osteoporosis pharmacotherapy. One commonly used definition of high fracture risk is a 10-year probability of hip fracture or combined major osteoporotic fracture of ≥3.0 or ≥20 percent, respectively (using the Fracture Risk Assessment Tool [FRAX]). However, this strategy has not been assessed in clinical trials. A reasonable alternative is to provide pharmacologic treatment to men with low bone mass (T-scores between -1.0 and -2.5) and any condition known to increase fracture risk (table 1) (eg, high-dose glucocorticoid therapy, gonadotropin-releasing hormone [GnRH] agonist therapy, frequent falls, prior organ transplantation), particularly if the underlying condition cannot be adequately addressed.

The FRAX criteria for pharmacologic intervention were chosen on the basis of a United States-specific economic analysis. Intervention thresholds have been estimated for other countries based upon assessment of absolute fracture risk and country-specific analyses and may be accessed directly from the FRAX website. As examples:

The 2010 Osteoporosis Canada guidelines recommend pharmacologic therapy for men (and women) with a high 10-year absolute risk (>20 percent probability for major osteoporotic fracture) and for individuals aged ≥50 years who have sustained a fragility fracture [20]. For individuals at moderate risk for fracture (10 to 20 percent), the decision to treat should be based upon the presence of additional risk factors not considered in the risk assessment system and upon individual preference.

In the United Kingdom, the National Osteoporosis Guideline Group recommends an age-dependent intervention threshold for men (and women), which ranges from 7.5 to 30 percent for ages 50 to 80 years [21].

In an analysis of data from a population-based cohort of 5880 older men (mean age 73.6 years), the proportion of men identified for osteoporosis treatment varied from 2.2 to 25.3 percent, depending upon the criteria used to assess osteoporosis and the risk for fracture [22]. Use of the BMD criteria proposed by the World Health Organization (WHO; femoral neck T-score ≤-2.5 derived from female reference database) identified the fewest men for osteoporosis treatment (2.2 percent), whereas use of the FRAX intervention thresholds set by the BHOF for men with BMD T-scores between -1 and -2.5 identified the most men for treatment (25.3 percent). During the 10-year follow-up period, 177 men (3 percent) had a hip fracture. The observed 10-year fracture probabilities were highest among the men identified as having osteoporosis by the WHO BMD criteria (20.6 versus 9.5 percent using FRAX thresholds set by the BHOF). Of note, the use of a male reference database (rather than a female reference database as proposed by the WHO) to calculate T-scores leads to the identification of many more men for treatment. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men", section on 'Diagnosis of osteoporosis' and "Overview of dual-energy x-ray absorptiometry", section on 'Reference databases'.)

Choice of therapy — Males and females seem to respond comparably to available osteoporosis pharmacotherapies, so the approach to treatment is generally similar. Nonetheless, few trials have evaluated the impact of pharmacologic agents on fracture risk reduction in men [23,24]. In the absence of high-quality, head-to-head drug comparison trials to determine the relative efficacy of the individual drugs, choice of therapy should be based upon efficacy, safety, cost, convenience, and other patient-related factors. Recommendations for initial treatment may differ for men with severe osteoporosis. (See 'Severe osteoporosis' below.)

Initial therapy: Bisphosphonates — For most men who require pharmacologic therapy, we suggest oral bisphosphonates as initial therapy because of their efficacy, favorable cost, and the availability of long-term safety data. In a meta-analysis of trials in men with osteoporosis, bisphosphonates reduced the risk of vertebral (six trials, relative risk [RR] 0.37, 95% CI 0.25-0.54) and nonvertebral (four trials, RR 0.60, 95% CI 0.40-0.90) fracture [25].

Among the available oral bisphosphonates, we (and others) suggest weekly alendronate or risedronate [12,20,26,27]. In randomized trials, alendronate and risedronate improved BMD and significantly reduced the risk of vertebral fracture [28-33]. As an example, in a two-year, open-label trial of 316 men with osteoporosis who were randomly assigned to risedronate (5 mg daily) or an active comparator group (alfacalcidol or vitamin D), the incidence of vertebral fractures was significantly lower in the risedronate group (9.2 versus 23.6 percent) [32]. In a meta-analysis of trials evaluating individual osteoporosis drugs in men with osteoporosis, there was a significant reduction in the risk of vertebral fractures with alendronate (two trials, RR 0.33, 95% CI 0.16–0.69) and risedronate (two trials, RR 0.43, 95% CI 0.24–0.75) [25].

The dosing, adverse effects, and the prescribing instructions designed to minimize gastrointestinal side effects of oral bisphosphonates are reviewed in detail elsewhere. (See "Bisphosphonate therapy for the treatment of osteoporosis", section on 'General Principles' and "Risks of bisphosphonate therapy in patients with osteoporosis", section on 'Risks specific to oral bisphosphonates'.)

Bisphosphonates are generally not recommended for individuals with an estimated glomerular filtration rate (eGFR) below 30 to 35 mL/min/1.73 m2, although the evidence upon which this practice is based is limited. Management of osteoporosis in people with chronic kidney disease is reviewed separately. (See "Osteoporosis in patients with chronic kidney disease: Diagnosis and evaluation" and "Osteoporosis in patients with chronic kidney disease: Management".)

Contraindications or intolerance to oral bisphosphonates — Intravenous (IV) bisphosphonates (zoledronic acid and ibandronate) are an alternative for individuals who cannot tolerate oral bisphosphonates or who find the IV dosing regimen more convenient. Zoledronic acid is the only IV bisphosphonate that has demonstrated efficacy for fracture prevention in men [34,35], and it is therefore our agent of choice.

Men who have esophageal disorders (achalasia, scleroderma involving the esophagus, esophageal strictures, varices), gastrointestinal intolerance to oral bisphosphonates, or an inability to follow the dosing requirements of oral bisphosphonates (including an inability to sit upright for 30 to 60 minutes and/or to swallow a pill) should not be treated with oral bisphosphonates. Oral bisphosphonates should also be avoided after certain types of bariatric surgery (eg, Roux-en-Y gastric bypass) due to uncertainty about medication absorption/bioavailability and theoretical risk for damage to surgical anastomoses within the gastrointestinal tract.

In the absence of direct fracture efficacy data for IV ibandronate, we prefer zoledronic acid based upon the following trials:

In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial, 2127 adults with hip fracture were randomly assigned to receive yearly zoledronic acid (5 mg) or placebo within three months of surgical repair [34]. Patients also received vitamin D, if the 25-hydroxyvitamin D [25(OH)D] concentration was <15 mg/dL or unknown, and calcium. After a median follow-up of 1.9 years, new fractures occurred in 8.6 and 13.9 percent of individuals in the zoledronic acid and placebo groups, respectively, representing a relative risk (RR) reduction of 35 percent (hazard ratio [HR] 0.65, 95% CI 0.50-0.84). All-cause mortality, a secondary safety endpoint, was lower in the zoledronic acid group compared with placebo group (HR 0.72, 95% CI 0.56-0.93).

In a separate trial, 1199 men with primary or hypogonadism-associated osteoporosis (mean T-score femoral neck -2.23, approximately 30 percent with prevalent vertebral fractures) were randomly assigned to zoledronic acid (5 mg IV) or placebo at baseline and 12 months [35]. All patients received calcium and vitamin D supplementation. After two years, there were fewer morphometric vertebral fractures in the zoledronic acid group (1.6 versus 4.9 percent in the placebo group, RR 0.33, 95% CI 0.16-0.70).

Prior to receiving IV bisphosphonates, patients should be assessed for hypocalcemia, vitamin D deficiency, and kidney impairment by measuring serum calcium, creatinine, and 25(OH)D. It is unclear what level of 25(OH)D is desirable prior to IV bisphosphonate infusion, although many experts recommend levels of at least 20 to 25 ng/mL (50 to 62 nmol/L). Additional information regarding dosing, adverse effects, and the prescribing instructions designed to minimize adverse effects is reviewed elsewhere. (See "Bisphosphonate therapy for the treatment of osteoporosis", section on 'IV regimen' and "Risks of bisphosphonate therapy in patients with osteoporosis".)

Contraindications/intolerance to any bisphosphonates — For men who cannot tolerate oral or IV bisphosphonates, options include bone anabolic agents (eg, teriparatide [PTH (1-34)], abaloparatide [parathyroid hormone-related protein (PTHrP) (1-34)]) or denosumab.

PTH/PTHrP analogsTeriparatide and abaloparatide are generally reserved for men who have failed previous therapy (eg, continue to fracture after one year of bisphosphonate therapy) or men with severe osteoporosis (low BMD [T-score <-2.5] and at least one fragility fracture, T-score of ≤-3.0 even in the absence of fractures, severe or multiple vertebral fractures). (See 'Severe osteoporosis' below and "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Choice of therapy'.)

Teriparatide – In the largest trial to date, 437 men with osteoporosis were randomly assigned to receive teriparatide (20 or 40 mcg/day by subcutaneous injection) or placebo. After 11 months of treatment, teriparatide increased spine and femoral neck BMD more than placebo (5.9 and 9 percent in the low- and high-dose groups at the spine; 1.5 and 2.9 percent in the low- and high-dose groups at the femoral neck) [36].

Abaloparatide – In a randomized trial of abaloparatide or placebo in 228 men whose mean lumbar spine T-score was -2.1, approximately 35 percent of whom had prevalent vertebral fractures, abaloparatide increased BMD at the lumbar spine and total hip more than placebo over 12 months [37]. The trial was not designed to assess fractures, which were infrequent in both groups.

After teriparatide or abaloparatide is discontinued, an antiresorptive agent should be administered to prevent discontinuation-associated bone loss, although the decline in BMD in men appears smaller than in women [38]. Contraindications, dosing, adverse effects, monitoring, and duration of teriparatide and abaloparatide therapy are reviewed separately. (See "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis".)

DenosumabDenosumab is a potent antiresorptive agent that may have a role for the treatment of osteoporosis in men who are intolerant of or unresponsive to other therapies and in those with impaired kidney function. Denosumab increases BMD in men with low bone mass [39], but it has not yet been shown to reduce fracture risk in men, except for men with prostate cancer receiving androgen deprivation therapy. (See "Side effects of androgen deprivation therapy", section on 'Osteoporosis and bone fractures'.)

Delaying or discontinuing denosumab therapy increases the risk of multiple rebound vertebral fractures, a phenomenon documented primarily in women but also reported in men [40]. This issue is reviewed in more detail separately. (See "Denosumab for osteoporosis", section on 'Discontinuation or delay of denosumab'.)

RomosozumabRomosozumab is an agent with mixed anabolic and antiresorptive properties that is being evaluated for the treatment of men with osteoporosis [41-43]. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Romosozumab'.)

In a randomized trial of romosozumab or placebo in 245 men with T-score ≤-2.5 or ≤-1.5 plus a history of fragility fracture, romosozumab increased BMD at the lumbar spine and total hip more than placebo over 12 months [41]. Fractures, reported as a safety outcome, were infrequent in both groups. There were more serious cardiovascular adverse events in men receiving romosozumab (4.9 versus 2.5 percent in the placebo group), although the increase was not statistically significant.

Severe osteoporosis — Men with severe osteoporosis at very high fracture risk may benefit from initial treatment with an agent with bone anabolic properties (typically teriparatide due to longer-term safety data), given evidence indicating maximization of bone density gains when anabolic agents are given prior to antiresorptive treatments [44], as well as data suggesting superiority of anabolic agents over antiresorptive agents for reducing vertebral fracture risk [45-47]. Abaloparatide and romosozumab are alternative anabolic agents. Abaloparatide has received regulatory approval in the United States for the treatment of men at high risk for osteoporotic fracture. Romosozumab is approved for use in men at high risk for fracture in some countries, but not in the United States [19]. (See "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Patient selection' and "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Selection of anabolic agent'.)

Factors that may indicate a very high fracture risk and thus warrant consideration of initial treatment with an anabolic agent are the following:

Very low T-score (eg, T-score of ≤-3.0) even in the absence of fracture(s)

T-score of ≤-2.5 plus a fragility fracture

Severe or multiple vertebral fractures

After teriparatide or other anabolic agent is discontinued, an antiresorptive agent should be administered, although bone loss after discontinuation of anabolic therapy may be less pronounced in men than women [38]. (See "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Management after teriparatide'.)

Combination therapy — Concurrent treatment with alendronate and teriparatide attenuates the ability of teriparatide to increase spine and hip BMD in men [48]. Thus, we do not recommend concurrent use of bisphosphonates with teriparatide for the management of osteoporosis. However, the immediate use of bisphosphonates after teriparatide is withdrawn may maintain or even increase BMD in men further [49]. (See "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Management after teriparatide'.)

MONITORING THE RESPONSE TO THERAPY — While there are a number of approaches to monitoring therapy, there is no consensus on the optimal approach. For patients starting on therapy, we typically obtain a follow-up dual-energy x-ray absorptiometry (DXA) of hip and spine after one to two years and, if bone mineral density (BMD) is stable or improved, we monitor less frequently thereafter. There may be limitations to the use of spine DXA in aging men due to interference from osteophytes and vascular calcifications on the spine measurement. The use of biochemical markers of bone turnover to monitor response to therapy is not well studied in men and is not routinely recommended.

Monitoring for the identification of patients who may require a change in therapy is reviewed elsewhere. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Monitoring response to initial pharmacotherapy'.)

DURATION OF THERAPY — There is currently no consensus on how long to continue bisphosphonate therapy in men. In postmenopausal women with osteoporosis, alendronate, risedronate, and zoledronic acid have been shown to reduce fracture risk for up to 10, 7, and 6 years, respectively. Due to concerns about possible long-term risks of bisphosphonates (see "Risks of bisphosphonate therapy in patients with osteoporosis"), many experts recommend a "drug holiday" in selected groups of women and in men. We suggest suspending bisphosphonate treatment for men who have taken alendronate for five years or who have received zoledronic acid once yearly for three years if their bone mineral density (BMD) is stable, they have not had previous fragility fractures, and they are at low risk for fracture in the near future. BMD should be monitored approximately every two years after suspending therapy, and therapy should generally be resumed if BMD declines significantly or if the patient develops a new fragility fracture.

This topic is reviewed in detail separately. (See "Bisphosphonate therapy for the treatment of osteoporosis", section on 'Duration of therapy'.)

The duration of teriparatide and abaloparatide is reviewed separately. (See "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Duration of therapy' and "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Management after teriparatide' and "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Management after abaloparatide'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Osteoporosis" and "Society guideline links: Clinical densitometry".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Osteoporosis (The Basics)" and "Patient education: Calcium and vitamin D for bone health (The Basics)")

Beyond the Basics topics (see "Patient education: Osteoporosis prevention and treatment (Beyond the Basics)" and "Patient education: Calcium and vitamin D for bone health (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Lifestyle measures – Important lifestyle measures include exercise, smoking cessation, counseling on fall prevention, and avoidance of heavy alcohol use for all men with osteoporosis. (See 'Lifestyle measures' above.)

Ensure optimal calcium and vitamin D intake – Although the optimal intake (diet plus supplement) has not been clearly established in men with osteoporosis, approximately 1000 to 1200 mg of calcium and 600 to 800 international units of vitamin D daily are generally suggested. In men with osteoporosis (T-score below -2.5) and inadequate dietary intake, we suggest calcium and vitamin D supplementation (Grade 2B). (See "Calcium and vitamin D supplementation in osteoporosis".)

The dose of calcium and vitamin D may vary in individuals with coexisting medical conditions. (See "Calcium and vitamin D supplementation in osteoporosis", section on 'Coexisting medical problems'.)

Management of underlying conditions – If osteoporosis is due to another condition (eg, testosterone deficiency), the underlying cause should be treated. (See 'Management of underlying conditions' above.)

Patient selection for osteoporosis pharmacotherapy

For men with osteoporosis (history of fragility fracture, or in men ≥50 years, a T-score below -2.5), we recommend osteoporosis pharmacotherapy (Grade 1B). (See 'Patient selection' above.)

For testosterone-treated hypogonadal men who have a high risk for fracture, we suggest the addition of osteoporosis pharmacotherapy to testosterone therapy (Grade 2C). High-risk groups might include hypogonadal men whose bone mineral density (BMD) T-score is ≤-2.5 after adequate testosterone replacement therapy for ≥2 years; men on high-dose glucocorticoids; men with frequent falls; men who have had a recent fragility fracture, particularly if BMD T-score is ≤-2.5 at any skeletal site; or men with T-scores ≤-3.0. (See 'Patient selection' above.)

For men aged ≥50 years with T-scores between -1.0 and -2.5 who are at high risk for fracture, we suggest osteoporosis pharmacotherapy (Grade 2B). A reasonable threshold for high risk that may be cost effective in some settings is a 10-year probability (using the Fracture Risk Assessment Tool [FRAX]) of hip fracture or combined major osteoporotic fracture of ≥3.0 or ≥20 percent, respectively. (See 'Patient selection' above.)

Choice of initial therapy – For osteoporosis pharmacotherapy in most men, we suggest bisphosphonates as first-line therapy (Grade 2B). We favor alendronate or risedronate over other available bisphosphonates because of clinical trial data demonstrating efficacy in men with osteoporosis. (See 'Initial therapy: Bisphosphonates' above.)

Men who have esophageal disorders, gastrointestinal intolerance to oral bisphosphonates, certain types of bariatric surgery (eg, Roux-en-Y gastric bypass), or an inability to follow the dosing requirements of oral bisphosphonates should not be treated with oral bisphosphonates and can be treated instead with intravenous (IV) bisphosphonate therapy. Zoledronic acid is the only IV bisphosphonate that has demonstrated efficacy for fracture prevention in men. (See 'Contraindications or intolerance to oral bisphosphonates' above.)

Teriparatide, abaloparatide, and denosumab are alternatives in men who are intolerant of or unresponsive to any bisphosphonate. (See 'Contraindications/intolerance to any bisphosphonates' above.)

Severe osteoporosis – For men who are at very high risk for fracture (eg, T-score ≤-2.5 and at least one fragility fracture, T-score of ≤-3.0 even in the absence of fractures, severe or multiple vertebral fractures), we suggest teriparatide (Grade 2B). More long-term safety data are available for teriparatide than for other anabolic agents. Abaloparatide and romosozumab are alternative anabolic agents. After non-bisphosphonate agents are discontinued, an antiresorptive agent should be administered to prevent discontinuation-associated bone loss. (See 'Severe osteoporosis' above and "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Patient selection' and "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Management after teriparatide' and "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Romosozumab'.)

Monitoring response to therapy – While there are a number of approaches to monitoring therapy, no consensus exists on the optimal approach. Patients can be monitored with BMD measurements, as is recommended for postmenopausal women. For patients starting on therapy, we typically obtain a follow-up dual-energy x-ray absorptiometry (DXA) of hip and spine after one to two years and, if BMD is stable or improved, we monitor less frequently thereafter. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Monitoring response to initial pharmacotherapy'.)

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Topic 2059 Version 32.0

References

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