Chronic respiratory disorders
Special attention should be given to the adverse effects of androgen deprivation therapy (ADT) administered for prostate cancer. Not only is bone loss, ranging from 6.5 % to 17.3 %, accelerated with ADT but in the first year of treatment alone, bone loss of 2–4 % occurs at the lumbar spine and hip . A 2013 Swedish study of the link between ADT, hip fracture, and risk of death demonstrated that hip fractures result in an additional 30 deaths per 1,000 person-years for men with prostate cancer on ADT compared to all men with prostate cancer, particularly in the first months following fracture—a finding that underlies the need for greater awareness of this interaction .
Another drug-induced form of osteoporosis stems from glucocorticoid medications: steroids used to treat inflammatory, allergic, and immunological illnesses, ranging from asthma to rheumatoid arthritis. For men, glucocorticoid therapy is used particularly in cases of chronic obstructive pulmonary disease (COPD), inflammatory bowel disease, and organ transplantation. A UK general practice database study revealed that even a small dose of 5 % mg prednisolone daily can lead to an increased fracture risk in as little as three months . Bone loss, primarily in the ribs and vertebra, increases until cessation of treatment and may be attributed to several factors, including direct effect of steroids on bone, muscle weakness or immobility, reduced absorption of calcium, decrease in testosterone levels, or a combination of these . Again, recognition of the risk of glucocorticoid therapy is the key to successful treatment.
Many of the other secondary causes of osteoporosis including excessive alcohol use, smoking, and calcium and vitamin D deficiency have been discussed in an earlier chapter. Gastrointestinal disorders that hinder absorption of essential nutrients, hypercalciuria that results in loss of too much calcium through urine, and prolonged bed rest or immobility must also be considered in the diagnosis of male osteoporosis. Below is a list of risk factors [5, 22]:
Increased age (especially after 70 years)
Low body weight (body mass index less than 20–25)
Weight loss of more than 10 % body weight
Androgen deprivation therapy
Previous fragility fracture
Spinal cord injury
Chronic obstructive pulmonary disease
Screening and Diagnosis
Although interest in male osteoporosis is growing, there is still a serious lack of awareness, on the part of both healthcare professionals and men themselves, of the threat posed by the disease. A delayed diagnosis of male osteoporosis is further exacerbated by the fact that bone mass density persists longer in men than in women and that osteoporosis may present with no symptoms until a fracture occurs. The American College of Physicians (ACP) was among the first organizations to develop a set of risk factors for identifying male osteoporosis, including age 70 and over (50 and over if a fracture has occurred); low body weight defined as body mass of <20–25 kg/m2, weight loss of >10 % compared with adult weight or weight loss in recent years, lack of physical activity as well as other risk factors discussed above. Based on a meta-analysis, it proposed that periodic individualized risk assessment in men be initiated before the age of 65. In addition to a complete physical exam and history, it also endorsed measurement of bone density with a dual-energy x-ray absorptiometry (DXA) scan of the spine and hip for men who are at increased risk of osteoporosis and are candidates for drug treatment . The results of a DXA scan are reported in terms of a T-score: the number of standard deviations that bone density is above or below that of a young healthy adult.
By using a simple, relatively new (2007) clinical prediction rule, primary care physicians are in a key position to advance early recognition of osteoporosis and thereby determine whether men 50–70 years might benefit from a DXA scan. The Male Osteoporosis Risk Estimation Score (MORES) incorporates three variables: ≤55 to ≥75 years of age; weight of ≤154 to ≥176 lb; history of COPD as well as both controllable and noncontrollable risk factors . In an analysis of a nationally representative sample of men (n = 2,995) aged 50 and older who participated in the National Health and Nutrition Examination Survey (NHANES), Shepard et al. identified 93 % of men with previously unrecognized osteoporosis and 44 % of men who would benefit from a confirmatory DXA scan . See Table 2. Another testing model, the Osteoporosis Self-Assessment Tool (OST) uses self-reporting age and weight, subtracting the age from the weight in kilograms and multiplying the result by 0.2 . A subsequent study employing MORES, conducted in a primary care setting with a smaller number of men (n = 346) ≥60 years, found a slightly lower prevalence of osteoporosis compared with the earlier study: 80 % in contrast to 93 % of men identified with osteoporosis and 33 % in contrast to 44 % referred for a DXA scan . Possible limitations included a more confined geographical area (the Texas Gulf Coast), the smaller cohort, and a potential bias toward more robust older men. Nonetheless, MORES is an inexpensive, easily administered and calculated tool applicable in a clinical setting, with the prospect of identifying male osteoporosis at an early stage .
Male Osteoporosis Risk Estimation Score (MORES)
Age ≤55 years
Age 56–74 years
Age ≥75 years
Presence of chronic obstructive pulmonary disease
Weight ≤154 lb
Weight 155–176 lb
Weight >176 lb
Recommendations regarding testing for male osteoporosis lack uniformity. The US Preventive Screening Task Force (USPSTF) finds insufficient evidence for assessing the risks and benefits of screening for male osteoporosis. However, the Endocrine Society in 2012  and NOF in 2014  have issued indicators for BMD testing including (1) men age 70 and older, regardless of clinical risk factors, (2) men age 50–69 with clinical risk factors for fracture, (3) all adults with a fracture after age 50, and (4) adults with conditions or medications associated with low bone mass or bone loss.
Reduced BMD in men is generally quantified by a T-score of −1.0 to −2.5 for osteopenia and −2.5 or less for osteoporosis, a grading system analogous to that used for women. As would be expected, the initial criteria for diagnosing osteoporosis, issued by the World Health Organization in 1994, were developed for women. Whether a male specific or a female specific T-score should be used for men has come under question. As Adler points out, for some time, DXA machines in the United States and most of the world used a male normative base for determining male T-scores. However, in recent years, the World Health Organization, the International Osteoporosis Foundation (IOF), and the International Society for Clinical Densitometry(ISCD) have endorsed the use of a white female database (NHANES III, Caucasian women aged 21–29) to obtain a BMD value at the femoral neck for both men and women . To obtain the most accurate reading, DXA results should be used in combination with the FRAX tool, which predicts a 10-year hip fracture rate based on a series of risk factors including age, gender, previous fragility fracture, T-score of ≤ −2.5 at the femoral neck or spine, low bone mass as indicated by a T-score between −1.0 and −2.5 at the femoral neck or spine, glucocorticoid treatment, smoking, excessive alcohol intake, other causes of secondary osteoporosis, and a 10-year probability of high fracture of ≥3 % . When DXA and FRAX are used together, it is likely that a larger number of older men will be identified for treatment under the new NOF guidelines. However, as Adler points out, while more men may be identified, there is no evidence indicating that men who show no signs of osteoporosis through DXA but have a high fracture risk by FRAX will respond to therapy .
Although other bone densitometry techniques exist, there is insufficient evidence that quantitative computer tomography (QCT), peripheral QCT (pQCT), or peripheral dual-energy x-ray absorptiometry (pDXA) can predict fracture risk in men . However, Bauer et al. found that validated heel quantitative ultrasound densitometry (QUS) mechanisms predict risk of hip and nonvertebral fracture in men 65 and older almost as well as does BMD .
In addition to the history, physical examination, BMD measurement, and FRAX assessment, a series of laboratory tests may be performed to determine correctable causes of bone loss. See Chapter 2. They include a complete blood count; serum chemistry levels, specifically calcium to detect hyperparathyroidism or hypocalcemia; phosphate, alkaline phosphatase and 25(OH) vitamin D to assess osteomalacia; creatinine levels for renal function; magnesium for calcium absorption and metabolism; liver function tests for alcohol abuse; thyroid-stimulating hormone (TSH) levels for thyroid dysfunction; and 25-(OH) vitamin D levels for vitamin D deficiency . See Table 3.
Suggested basic and advanced laboratory testing for osteoporosis in men
Initial laboratory tests
Advanced laboratory tests
Serum calcium, phosphorus, BUN, and creatinine
24 h urine cortisol and urine creatinine
Liver enzymes including alkaline phosphatase
Markers of bone formation:
Bone specific alkaline phosphatase; procollagen N-1 terminal propeptide
Serum vitamin D25 OH and intact parathyroid hormone (PTH)
Markers of bone loss:
Urine N-terminal telopeptide
Serum testosterone and luteinizing hormone
Immunological tests for sprue
Full panel of thyroid function tests
It has long been recognized that men have a higher prevalence of secondary osteoporosis than do women; for example, a recent study of 234 men at a mean age of 70.6 years found secondary osteoporosis in 75 % of the cohort . Tests for secondary causes include 24-hour urine calcium level for hyper-and hypocalciuria, indicating possible vitamin D deficiency, parathyroid hormone level for hyperparathyroidism, and testosterone and gonadotropic levels in younger men with reduced bone mass for sex hormone deficiencies .
Biochemical markers of bone formation and resorption have been examined to determine their value in predicting fracture risk in men; however, given available evidence, they are not considered to be a replacement for DXA measurements. Although NOF guidelines state that biochemical markers may predict risk of fracture, the results of other studies are promising but inconclusive and conflicting. For example, in the Dubbo Osteoporosis Epidemiology Study, only one bone turnover marker, carboxyterminal cross-linked telopeptide of type 1 collagen (S-ICTP), was associated with high bone resorption and increased risk of fracture, independent of BMD . Bauer et al. conducted a sub analysis of the Osteoporosis Fracture in Men (MrOS) study cohort (n = 947 randomly selected from the original 5,995 men), focusing on the relation between elevated bone turnover markers (BTMs) and the risk of hip and other nonspine fractures. Bone markers used were formation marker PINP, resorption marker βCTX, and osteoclast number marker (TRACP5b). Findings indicated that elevated serum levels of these markers were related to a higher rate of hip bone loss in older men, but the link was insufficient to predict fracture accurately. Moreover, after accounting for baseline BMD, none of the relationships between BTMs and fracture were statistically significant, leading to their conclusion that BTMs should not be included in risk stratification tools for men . The MINOS study, reported a year earlier, also found no association between high bone turnover and increased fracture risk in men ≥50 and stressed that BTMs cannot be used to predict male fractures in clinical practice .
In the absence of additional research and despite their seeming advantages in terms of low cost and noninvasiveness, BTMs are contraindicated as a predictive tool for male osteoporosis in routine clinical practice. Current efforts to establish and implement international consensus reference standards, using s-PINP as the bone formation marker and s-βCTX as the resorption marker in all clinical trials, are an important steps in advancing the clinical utility of BTMs in both predicting and managing osteoporosis .
Because vertebral fracture is consistent with a diagnosis of osteoporosis quite apart from BMD measurement, the NOF recommends vertebral imaging in men age 80 and older if BMD T-score at the spine, hip, and femoral neck is ≤ −1.0; at age 70–79 if BMD T-score is ≤ −1.5, and −3.0; and at age 50 and older with low-trauma fracturing during adulthood, height loss of 1.5 inches or more; prospective height loss of 0.8 inches or more; and recent or ongoing long-term glucocorticoid treatment. Since most densitometers can also perform vertebral imaging, the tests can be done concurrently.
Strategies to prevent osteoporosis are not significantly different in men and women, but just as male osteoporosis is not as widely recognized, preventative and therapeutic measures are not broadly prescribed and implemented. Here the healthcare professional plays a key role in ensuring that risk factors for osteoporosis are an important part of regular physical examinations. Adequate calcium and vitamin D are key factors in preventing osteoporosis. In terms of calcium intake, the NOF recommends a daily dose of 1,000 mg for men aged 50–70, with 1,200 mg daily for men 71 and older. For vitamin D, the NOF recommendation is 800–1,000 international units (IU) for all adults age 50 and older, while the Institute of Medicine advocates a lower dose of 600 IU per day until age 70, and then 800 IU per day for ages 71 and older. In a 1997 study, Dawson-Hughes et al. demonstrated that in both men and women age 65 and older, calcium and vitamin D supplementation reduced bone loss moderately over a 3-year period and reduced the incidence of nonvertebral fractures; in men, a significant effect at the hip, spine, and total body was evident . A subsequent study involving 2017 men and 649 women, aged 65–85, confirmed these findings, with results indicating a 22 % reduction in total fracture incidence and a 33 % reduction in fractures at major osteoporotic sites . For patients at risk of a vitamin D deficiency, the goal is to maintain serum 25 (OH) levels at or above 30 ng/ml to ensure optimal skeletal health .
Smoking cessation, whether undertaken individually or in monitored cessation programs, alcohol intake of no more than two drinks per day, and weight-bearing exercise programs, including jogging, walking, weight lifting, dancing, and other aerobic sports are all recommended preventative measures for males. In terms of smoking, a 1996 analysis of the Framingham Heart Study cohort (which at that point had prospectively collected 40 years of data on smoking) determined that smoking at any stage of life produced adverse effects on the male skeleton. In particular, men who smoked at any point in life had a lower BMD at all skeletal sites; male smokers who had quit <10 years prior to the study had lower BMD than those who had quit ≥10 years prior . A more recent study confirms that smoking is a much stronger risk factor for fracture in men than in women, as well as a stronger and more lasting risk factor than previously determined. However, the risk is reversible: in the first 10 years following cessation, the risk is cut in half and no independent association has been found between risk fracture and duration of smoking .
Excessive alcohol not only reduces the body’s calcium reserves and increases cortisol levels but also results in the production of less testosterone which, in turn, restricts bone formation. Chronic alcoholism in men induces lower bone density in the femoral neck and trochanter with a significant inverse correlation between the amount of alcohol consumed and the degree of bone loss . Alcohol can also compromise balance and gait, leading to increased risk of falls and fractures.
Lack of physical exercise, application of casts to treat fractures, prolonged bed rest, and various forms of immobilization, from stroke and other types of paralysis to weightlessness in space, can be precipitating factors for what is generally known as “disuse osteoporosis” . As calcium leaches out of the bone, calcium excretion in the urine becomes four to six times higher than normal within three weeks of immobility. Because bones are no longer engaged in weight-bearing, they lose density; indeed, bone density of the vertebral column decreases by 1 % per week of bed rest, which is nearly 50 times greater than that of normal age-related bone loss .
Regular and lifelong exercise can help to ensure bone strength, improve balance, and halt or slow the progression of osteoporosis. Exercise for even a half hour per day strengthens muscles, works to preserve and increase bone mass, and improves coordination and balance. The three basic types of exercise for male osteoporosis are weight-bearing, resistance, and flexibility. High-impact weight-bearing exercises, including hiking, jogging, jumping, dancing, tennis, and aerobic sports, more generally, build and maintain bone strength, whereas swimming and cycling are not as effective. Running improves BMD but can be detrimental in cases of high mileage. A study by Hetland et al. indicates that male long-distance runners (N = 120, 19–56 years old) who logged up to 100 miles per week had reduced bone mass and increased bone turnover compared to controls . It confirms similar findings by MacDougall et al.  that bone density in long-distance male runners with mileage at 60–70 miles/week is lower than in men in a 15–20 mile group—the so-called endurance paradox. Mussolino et al. demonstrated that jogging is also associated with significantly higher femoral BMD in young and middle-aged men—a finding that may be of public health importance because femoral BMD is a strong predictor of hip fracture. The similarity in femoral BMD between those who jogged more than nine times a month and those who jogged less frequently again underscored the existence of a ceiling effect on the distance needed to improve BMD .
For those unable to undertake high-impact exercise, the NOF recommends brisk walking, low-impact aerobics, and the use of stair-step and elliptical training machines. The elderly can also benefit from such weight-bearing exercises as squats and leg presses, yoga and Tai Chi, and standing on one leg. In a study of elderly women but with results applicable to men, Finnish researchers identified a number of “impact exercises” to slow the progression of osteoporosis, including jumping, feet stomping, knee bends, leg lifts, and stair climbing . Resistance exercises ranging from lifting weights and using elastic exercise bands to functional movement such as rising up on your toes preserve bone calcium and increase muscle strength. Flexibility exercises such as yoga, Pilates, and Tai Chi can strengthen legs and improve balance; combined with evidenced-based fall prevention efforts and hip protectors, they can decrease risk of falls and fractures .
Finally prevention of male osteoporosis should take into account underlying medical conditions and medications such as glucocorticoid treatment that is known to cause bone loss. Early recognition can lead to effective treatment.
A judgment on when treatment for osteoporosis should be initiated is based on the series of factors determined by the physical examination and history, DXA findings, and FRAX results, and, to a limited extent, BTM levels.
As FDA recommendations demonstrate, it cannot be assumed that anti-osteoporotic drugs for women will be equally effective in men, and indeed thus far the FDA has approved only five medications for men—the bisphosphonates: alendronate, risedronate, and zoledronic acid; the anabolic agent: parathyroid hormone (teriparatide) and, most recently, the monoclonal antibody to RANKL: denosumab. Bisphosphonates have a high affinity for bone mineral but not for other tissues. They attach to bone surfaces, are incorporated into sites of bone remodeling, and suppress bone resorption . Although bisphosphonates have been shown to reduce fragility fractures in women, males experience positive effects primarily in terms of an increase in BMD and a decrease in both bone resorption and bone formation markers; nonetheless, these findings serve as the basis for justifying the use of bisphosphonates in men . Bisphosphonates also produce BMD changes in men with low testosterone levels as well as in those with normal levels.
In one of the key studies of alendronate therapy for male osteoporosis, Orwoll et al. found that 10 mg of alendronate over two years decreased bone turnover and increased bone density of the spine, hip, and total body—results that were evident within six months of initiating treatment. Moreover, using quantitative methods, they also found an incidence of vertebral fractures in only 0.8 % of the alendronate group as opposed to 7.1 % of men in the placebo group—an outcome consistent with the results of similar studies in postmenopausal women. A positive relationship between alendronate and hip fractures in men has yet to be determined. Because alendronate increases BMD in patients with low testosterone as well as in those with normal levels, it may be effective in hypogonadal and gonadal men. The ability of alendronate to reduce height loss—a nonsignificant 0.6 mm in alendronate group compared to 2.4 mm in placebo group—is also consistent with anti-fracture efficacy .
Alendronate is effective in cases of androgen deprivation therapy (ATP) for prostate cancer, glucocorticoid-induced osteoporosis (GC), and immobilization. To counteract the risk of bone loss and fracture in ATP patients with severe osteopenia or osteoporosis, a dose of 70 mg/week significantly increased BMD at the lumbar spine and femoral neck and markedly decreased the risk of femoral risk fracture . In an analysis of the benefits of early and sustained therapy, Greenspan and colleagues determined that treatment with 70 mg/week should be initiated early in the course of ADT and continued for at least two years .
Glucocorticoids are immunosuppressive drugs generally prescribed for men with inflammatory bowel disease, chronic obstructive pulmonary disease, organ transplantation, and, should the need arise, inflammatory arthritis. However, they inhibit bone formation and increase the risk of spine and hip fracture. In addition to adequate amounts of calcium and vitamin D, alendronate 70 mg/week for a year significantly increased lumbar spine (2.45 %), trochanter (1.27 %), total hip (0.75 %), and total body BMD (1.70 %) in patients taking glucocorticoids compared with placebo; biochemical markers of bone remodeling also decreased . Finally, the efficacy of alendronate has been proven in cases of disuse immobilization both on the ground and in space. A ground-based test of men consigned to bed rest for 17 weeks revealed no loss of BMD, decreased bone formation markers, and decreased or only slightly elevated bone resorption markers in the treated group as opposed to an untreated group . An analogous study of International Space Station crew members indicated that alendronate, in combination with exercise devices, lessened anticipated losses in bone mineral density of the spine, hip, and pelvis as well as in trabecular and cortical bone mass in the hip—a benefit applicable to patients on earth .
Second to alendronate in terms of prescribed bisphosphonates is risedronate. Risedronate tablets are prescribed for men with osteoporosis, particularly for those on. In a 2-year study of the use of risedronate 5 mg daily (coupled with calcium and vitamin D supplementation) by men with primary and secondary osteoporosis, the incidence of new vertebral fractures in the risedronate group was significantly reduced (9.2 %) compared to control (23.6 %), and the occurrence of nonvertebral fractures also declined (11.8 %) versus control (22.3 %). BMD at the lumbar spine, femoral neck, and total hip improved markedly, while loss of height and back pain decreased—all indicating that risedronate can be effective for a term of at least two years . Using risedronate 35 mg/week and comparable calcium and vitamin D supplementation, a double-blind 2-year study with placebo demonstrated the rapid efficacy of risedronate, with significant BTM decreases as early as three months and BMD increases as early as six months. In an open-label, 2-year extension of this study, risedronate continued to be well tolerated and to produce significant increases in lumbar spine BMD (7.87 % from baseline) in those patients who took the drug for four years—a finding similar to that of postmenopausal women treated with risedronate for the same time period. The generally accepted term is now 3–5 years.
With respect to corticosteroid-induced osteoporosis, treatment with risedronate 5 mg for 12 months increases BMD in both men and women receiving high doses of the treatment, with a 2.5 mg dose being less effective; combined data for both the 2.5 and 5 mg groups reveals a 70 % reduction in vertebral fracture incidence . A subsequent study indicated that daily treatment with risedronate decreased vertebral fracture risk within one year in men receiving corticosteroids . Further studies are needed to provide clarification on the comparative effectiveness of not only alendronate versus risedronate but of all medications used for osteoporosis.
Although prescribed for women to prevent and treat postmenopausal osteoporosis, the bisphosphonate, ibandronate, is not FDA approved for men. In a 2010 trial, the STudy Researching Osteoporosis iN Guys (STRONG), conducted over a 1-year period, men receiving oral ibandronate experienced a significantly greater increase in lumbar spine BMD than those taking placebo (3.5 % vs. 0.9 %) as well as increases at the total hip, femoral neck, and trochanter . However, ibandronate can cause serious problems in the stomach and esophagus and requires the patient to sit upright or stand for one hour after administration. Despite their effectiveness, oral bisphosphonates have several disadvantages; they can cause gastrointestinal distress in some patients and require frequent dosing. These factors potentially contribute to a detrimental effect on drug adherence.
The most studied of the intravenous bisphosphonates, zoledronic acid, was approved by the FDA in 2008 as, thus far, the only treatment shown to reduce the incidence of fracture and mortality in patients with a previous low-trauma hip fracture. The FDA cited the results of the HORIZON Recurrent Fracture Trial in which men ≥50 years of age comprised 24 % of a cohort of 2,126 patients: all had experienced low-trauma hip fracture and could not tolerate oral bisphosphonates. A once yearly 5 mg dose of zoledronic acid age administered 90 days after surgical repair of a hip fracture reduced the rate of a new clinical, but not hip, fracture, by 35 %, while increasing total hip and femoral neck BMD after 36 months in both men and women compared with the placebo group. It also decreased the all-cause mortality by 28 %, perhaps in part because of the reduction in new fractures . Further research determined that the optimal time for zoledronic acid infusion was 2–12 weeks following fracture repair . In the first male osteoporosis trial with fracture as an end point, participants experienced primary osteoporosis or osteoporosis due to hypogonadism, with one or more vertebral fractures at baseline; results showed that two annual infusions of zoledronic acid reduced the risk of new morphological vertebral fractures by 67 %—a result similar to that for postmenopausal women . Further evidence is needed to determine the efficacy of bisphosphonates for nonvertebral and hip fractures in men.
Unlike the antiresorptive therapies outlined above, the parathyroid hormone, teriparatide, is the only approved agent that increases bone formation in male osteoporosis. It is self-injected in a recommended dose of 20 mcg/day for no more than 24 months. A study (n = 437) indicating higher BMD at the spine and femoral neck for those on teriparatide  was followed by an analysis of a portion of the same population (n = 355) at 30 months posttreatment. Following discontinuation of teriparatide, BMD gradually decreased but lumbar spine and total hip values remained higher than at baseline; although the risk of vertebral fractures fell by a nonsignificant 51 %, the incidence of moderate or severe fractures was significantly reduced by 83 %. It is important to note that the administration of bisphosphonates following withdrawal from teriparatide maintains and even leads to increased BMD .
Combination therapies involving teriparatide and antiresorptive agents designed to increase bone mass and strength have yet to be proven safe and effective. Thus far, it is known that alendronate combined with teriparatide hinders the ability of teriparatide to induce bone formation at the lumbar spine and femoral neck , whereas risedronate combined with teriparatide increases BMD at the total hip and femoral neck to a greater extent than either therapy alone; at 18 months, lumbar spine BMD increased for all three groups but with no significant difference among them . Forthcoming research on fracture outcomes should provide greater insight into the potential efficacy of combination therapies for osteoporosis.