Commentary: Male Osteoporosis—Policy Gaps in Prevention and Treatment

Osteoporosis is a disabling disease affecting 10 million Americans, leading to increased risk of fractures and poor functional ability. Although typically thought of as a women's disease, millions of men are diagnosed with osteoporosis or low bone mass, and the risk for osteoporotic fractures is increasing. To address undetected and untreated osteoporosis among men, public health education should be targeted to males. Insurance programs, including Medicare, should add the heel qualitative ultrasound (QUS) for age-eligible men with follow-up every 2 years. Policy changes should address funding of targeted education and prevention programs for aging males, including coverage of screening tests.     

The use of selective estrogen receptor modulators on bone health in men

Selective estrogen receptor modulators (SERMs) represent a class of drugs that act as agonist or antagonist for estrogen receptor in a tissue-specific manner. The SERMs drugs are initially used for the prevention and treatment of osteoporosis in postmenopausal women. Bone health in prostate cancer patients has become a significant concern, whereby patients undergo androgen deprivation therapy is often associated with deleterious effects on bone. Previous preclinical and epidemiological findings showed that estrogens play a dominant role in improving bone health as compared to testosterone in men. Therefore, this evidence-based review aims to assess the available evidence derived from animal and human studies on the effects of SERMs on the male skeletal system. The effects of SERMs on bone mineral density (BMD)/content (BMC), bone histomorphometry, bone turnover, bone strength and fracture risk have been summarized in this review.     

Role of bisphosphonates in the management of postmenopausal osteoporosis: an update on recent safety anxieties

Following their introduction in the 1990s, bisphosphonates have become the mainstay of treatment in the management of postmenopausal osteoporosis, and their use continues to rise. Commonly noted adverse effects in clinical practice include gastrointestinal side-effects, acute phase reactions (predominately seen with intravenous preparations) cutaneous reactions and more rarely, ocular side-effects. However, recent reports of potentially serious adverse effects of bisphosphonate therapy, including atypical subtrochanteric and femoral shaft fractures, atrial fibrillation, oesophageal carcinoma and osteonecrosis of the jaw, have prompted concerns regarding the long-term safety of this class of drugs. This review summarizes the benefits and potential adverse effects of bisphosphonates used in the treatment of postmenopausal osteoporosis. Although evidence of a definitive casual relationship between bisphosphonate therapy and serious adverse effects is lacking, concern remains particularly in relation to atypical subtrochanteric and femoral shaft fractures. This has important consequences in terms of determining optimum duration of therapy and how best to target therapy at those most at risk. Recently, attention has focused on individual fracture risk assessment in order to optimize the risk-benefit ratio of treatment for individual patients. A review of the role of hormone replacement therapy in younger women with significant risk of osteoporotic fractures may be timely in these circumstances.     

The microanatomy of trabecular bone in young normal and osteoporotic elderly males

Normally there is a gradual continual loss of cortical and trabecular bone in both men and women as they age. Osteopenia and osteoporosis are conditions in which the loss results in brittle bones that fracture easily. Males with low testosterone and hypogonadism are predisposed to osteoporosis and prevention tends to be overshadowed by the greater problem in postmenopausal women. The ability of the skeleton to resist external forces depends partly upon the amount of bone present and partly upon other factors including cancellous bone microarchitecture. This is examined in iliac crest bone biopsies from idiopathic osteoporotic men, mean age 60 ± 12 SD years [n = 16]. These were compared with a healthy control group (autopsy samples), mean age 30 ± 8.9 years [n = 28] with the aim of examining the pattern of cancellous atrophy in male idiopathic osteoporosis. Undecalcified specimens were embedded in methylmethacrylate and prepared for histomorphometry. Sections were analysed using an automated trabecular analysis system (TAS), whereby a binary image was created. Area measurements including the trabecular surface and distance measurements including the trabecular width were made. The binary image was thinned to its medial framework and the node and terminus number as indices of trabecular interconnection were recorded, together with the strut length. Results (median (range)) showed a lower percentage bone volume in the elderly osteoporotic male, 10.2% (5.4–23.1) compared to young normals 25.2% (14.6–43.9), p < 0.001. The trabeculae tended to be thinner, 95.7 µm (66.7–170.7) c.f. 120.8 µm (75.8–208.6) and considerably fewer in number, 11.1 (2.1–31.4) c.f. 48.3 (25.4–66.9), p < 0.001 per field and in particular the number of nodes, 2.1 (0.15–14) c.f. 40.6 (10.3–74.1) per field and the node: terminus ratio fell to 0.13 (0.01–1.19) c.f. controls 0.98 (0.24–6.69), p < 0.001. It was concluded that the pattern of cancellous atrophy in male idiopathic osteoporosis differs from normal aging and resembles that in postmenopausal women. Results using the automated TAS confirm previous observations made manually.     

The predictive role of bone turnover markers for BMD in middle-aged men

Measurement of bone turnover markers has been proposed as a potentially valuable clinical laboratory aid in osteoporosis risk assessment. These markers may allow quantitative evaluation of rates of bone loss, and thereby identify persons at risk for osteoporosis at an earlier stage. As far as we know, this is the longest longitudinal study on bone turnover markers conducted in adult men. The objectives of this study were to determine whether markers of bone formation (type I procollagen amino-terminal propeptide, PINP, and carboxy-terminal propeptide, PICP), and of bone resorption (type I collagen carboxy-terminal telopeptide, ICTP), are predictive of changes in lumbar spine and femoral neck BMD over a 5-year period, and to determine the ability of the bone resorption marker urine amino-terminal telopeptide (NTx) to explain the variance in BMD change over the past 5 years in a group of men 35–69 years old. In this group, NTx was the only marker to correlate significantly with BMD changes at the femoral neck (r = ?0.21), but not at the spine. The use of the biochemical markers studied to predict change in bone density in adult men in middle-aged years is of very limited value.     

Calcium and vitamin D--for whom and when

The basis of 'nutritional' interventions for the prevention of postmenopausal osteoporosis and osteoporotic fracture is a large topic with much genetic and biochemical evidence, as well as the results of randomized controlled trials, to guide the investigator and clinician. The efficacy of treatment with calcium and vitamin D was once controversial, but with the advent of controlled clinical trials using bone mineral density as an endpoint it has become clear that calcium with or without vitamin D therapy can lead to reductions in the rate of bone loss in postmenopausal women of all ages. Furthermore, with certain caveats, calcium with vitamin D therapy in the older postmenopausal woman can lead to useful reductions in fracture rates and falls, especially in populations with reduced exposure to sunlight, which is potentially the majority of postmenopausal women in both developed and developing countries. However, estrogen, selective estrogen receptor modulators (SERMs) and bisphosphonates (especially when given in combination with calcium and vitamin D) are more efficacious in preventing fracture, particularly in postmenopausal patients with impaired bone structure.     

LOH–pitfalls of an ambiguous abbreviation

Osteoporosis in elderly men is becoming an important health issue with the aging society. Elderly men with androgen deficiency are exposed to osteoporosis and can be treated with testosterone replacement. In this study, Eurycoma longifolia (EL), a plant with androgenic effects, was supplemented to an androgen-deficient osteoporotic aged rat as alternative to testosterone. Aged 12 months old Sprague-Dawley rats were divided into groups of normal control (NC), sham-operated (SO), orchidectomised-control (OrxC), orchidectomised and supplemented with EL (Orx?+?El) and orchidectomised and given testosterone (Orx?+?T). After 6 weeks of treatment, serum osteocalcin, serum terminal C-telopeptide Type 1 collagen (CTX) and the fourth lumbar bone calcium were measured. There were no significant differences in the osteocalcin levels before and after treatment in all the groups. The CTX levels were also similar for all the groups before treatment. However, after treatment, orchidectomy had caused significant elevation of CTX compared to normal control rats. Testosterone replacements in orchidectomised rats were able to prevent the rise of CTX. Orchidectomy had also reduced the bone calcium level compared to normal control rats. Both testosterone replacement and EL supplementation to orchidectomised rats were able to maintain the bone calcium level, with the former showing better effects. As a conclusion, EL prevented bone calcium loss in orchidectomised rats and therefore has the potential to be used as an alternative treatment for androgen deficient osteoporosis.     

Prevalence of low forearm bone mineral density in Bulgarian men: a pilot study

Objective. To determine the prevalence of osteoporosis at the distal forearm in a male cohort referred for bone density testing and to compare it to published data of Bulgarian women.

Design and subjects. 315 consecutive Bulgarian men aged 20 to 84 years were included (mean age 53.74 ± 14.67 years). 59% of them were self-referrals. The comparative female group consisted of 8869 Bulgarian women whose forearm bone mineral density (BMD) was measured in another study.

Measurements. BMD was measured by single X-ray absorptiometry at the distal forearm (distal and ultradistal sites) in all men. T-scores were calculated from manufacturer-provided Danish male reference data.

Results. The ratio of female to male patients was 28.2 (8869 to 315). Peak BMD was observed in men aged 30 to 39 years: 0.560 ± 0.065 g/cm² (distal site) and 0.490 ± 0.070 g/cm² (ultradistal site). A steady BMD decline followed reaching 0.492 ± 0.064 g/cm² at the distal and 0.412 ± 0.069 g/cm² at the ultradistal site in age group >70. Age had a rather weak negative impact on forearm BMD described by a linear model. In men aged over 50 years the prevalence of osteoporosis at the distal site was 21.19%, compared to 20.45% in women. Low bone mass was seen in 48.77% of men and 32.50% of women. Normal BMD was more frequent in women (47.05%) than in men (30.04%).

Conclusions. We found a high prevalence of forearm osteoporosis in Bulgarian men which is comparable to that already known in women.     

Osteoporosis, falls and exercise

Osteoporosis, a manifestation of bone atrophy that leads to great susceptibility to fractures, is a very important public health problem today because of its great morbidity, mortality and important economic repercussions. It is a problem that will tend to become more serious with the increase in the number of elderly persons. Bone mass is gained during adolescence, reaches a plateau during the third decade and remains stable until approximately age 50, after which a progressively gradual loss is observed. There is no real cure for osteoporosis, but a series of strategies can be used to reduce bone loss and improve bone mass. Osteoporosis has been considered a disease that accompanies the process of ageing; however, this fatalistic attitude should be discarded, as it is possible to correct and decrease the risk factors. Intervention strategies are based on three pillars: nutrition, physical activity and pharmacological agents. Physical activities and exercise programmes are important because they not only can counter the loss of bone mass but also improve neuromuscular capacity, maintaining and increasing strength and muscle mass, which can help to avoid falls and reduce their impact and consequences. The general principles that apply to any exercise programme also apply to preventing bone mass loss. They also can be applied to persons with osteoporosis. However, to understand the peculiarities of these programmes, the propensity for suffering fractures of these former groups should be kept in mind. Special care should be taken to avoid falls and injuries. Weight-bearing exercise and resistance training are recommended for the prevention programmes. Other activities such as tai-chi, dancing, gymnastic or callisthenic exercises can help to improve balance, gait and muscle coordination and diminish the risk of falling. These programmes should be complemented with postural education and a series of safety precautions.     

Clinical effects of growth hormone on bone: a review

Growth hormone (GH) stimulates bone turnover. Deficiency of GH due to hypopituitarism is related to low bone mineral density and increased fracture risk. GH substitution increases and thus normalizes bone mineral density in these patients, which is one of a number of arguments for GH substitution in hypopituitarism. In contrast, a possible therapeutic use of GH in idiopathic osteoporosis and glucocorticoid-induced osteoporosis is speculative and not established. Reduction of osteoporosis risk is an argument brought up for a use of GH in healthy elderly persons (anti-aging medicine). However, since only very limited data are available yet, this cannot be based on scientific evidence, and there are important concerns about the safety of use of GH in healthy elderly persons.     

Bazedoxifene: a new selective estrogen receptor modulator for postmenopausal osteoporosis

An ongoing need for safe and effective pharmacological therapies exists for postmenopausal osteoporosis, which imposes a significant burden on both women and the health-care system. Bazedoxifene is a novel selective estrogen receptor modulator with a unique tissue-selectivity profile. In phase 3 clinical trials of nearly 10,000 postmenopausal women, bazedoxifene was shown to significantly reduce the risk of new vertebral fracture versus placebo, with favourable effects on bone mineral density, bone turnover markers and the lipid profile. Moreover, in a subgroup of women at increased risk of fracture, bazedoxifene significantly decreased non-vertebral fracture risk versus both placebo and raloxifene. Bazedoxifene has been shown to be safe and well tolerated, with no evidence of endometrial or breast stimulation. These data suggest that bazedoxifene may offer significant clinical benefit for postmenopausal women with or at risk of developing osteoporosis, which may subsequently lessen the medical and economic burden of this disease.     

Osteoporosis: an invisible, undertreated, and neglected disease of elderly men

This article highlights a silent disease that threatens the health and vitality of older men. Among elderly men and women, osteoporosis is among one of the leading causes of morbidity and mortality in the United States. Once perceived as only a female dominated disease, osteoporosis is now known to be gender blind. The following discussion will review the epidemiology and pathology of osteoporosis, and identify the concerns raised for men, including neglect. Special management considerations for older men and recommendations for future research into this overlooked major health problem will be explored. Better understanding of how osteoporosis affects older men may help to encourage prevention strategies earlier in life, appropriate screening and monitoring, as well as more effective treatment later in life.     

The Health Belief Model and the Contraceptive Behavior of College Women: Implications for Health Education

Abstract

“The Incidence of Primary Cardiac Arrest During Vigorous Exercise,” David S. Siscovick, et al. To examine the risk of primary cardiac arrest during vigorous exercise, we interviewed the wives of 133 men without known prior heart disease who had had primary cardiac arrest. Cases were classified according to their activity at the time of cardiac arrest and the amount of their habitual vigorous activity. From interviews with wives of a random sample of healthy men, we estimated the amount of time members of the community spent in vigorous activity.

Among men with low levels of habitual activity, the relative risk of cardiac arrest during exercise compared with that of other times was 56 (95% confidence limits, 23 to 131). The risk during exercise among men at the highest level of habitual activity was also elevated, but only by a factor of 5 (95% confidence limits, 2 to 14). However, among the habitually vigorous men, the overall risk of cardiac arrest—i.e., during and not during vigorous activity—was only 40% that of the sedentary men (95% confidence limits, 0.23 to 0.67).

Although the risk of primary cardiac arrest is transiently increased during vigorous exercise, habitual vigorous exercise is associated with an overall decreased risk of primary cardiac arrest. (New England Journal of Medicine 1984;311:874-7.)

“Osteoporosis in Women with Anorexia Nervosa,” Nancy A. Rigotti, et al. Because estrogen deficiency predisposes to osteoporosis, we assessed the skeletal mass of women with anorexia nervosa, using direct photon absorptiometry to measure radial bone density in 18 anorectic women and 28 normal controls. The patients with anorexia had significantly reduced mean bone density as compared with the controls (0.64 ±0.06 vs. 0.72 ±0.04 g per square centimeter, P < 0.001). Vertebral compression fractures developed in two patients, and bone biopsy in one of them demonstrated osteoporosis. Bone density in the patients was not related to the estradiol level (r = 0.02). Levels of parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal despite low calcium intakes.

The patients with anorexia who reported a high physical activity level had a greater bone density than the patients who were less active (P < 0.001); this difference could not be accounted for by differences in age, relative weight, duration of illness, or serum estradiol levels. The bone density of physically active patients did not differ from that of active or sedentary controls.

We conclude that women with anorexia nervosa have a reduced bone mass due to osteoporosis, but that a high level of physical activity may protect their skeletons. (New England Journal of Medicine 1984;311:1601-6.)     

Arsenic exposure associated with decreased bone mineralization in male

Abstract

Objective: Arsenic (As) exposure may cause several medical problems. There were a few studies investigated whether it has affected bone tissue in women. However, there was no study in men. The aim of this study was to evaluate associations between bone mineral density (BMD) and As exposure in men subjects.

Material and methods: We enrolled in this study 254 subjects who due to chronic As exposure suspected and 82 subjects as a control group. Hair As levels were detected by a hair analysis (Varian AA240Z Zeeman Atomic Absorption Spectrometer, USA). BMD measurements were obtained using dual-energy X-ray absorptiometry instrumentation. We investigated associations between the hair As levels and BMD measurements.

Results: The frequency of osteoporosis and osteopenia was found to be 0.8% and 54.5%, respectively, in the As exposure group. The frequency of osteoporosis was found to be 1% and osteopenia was 32.4% in control subjects. There was significant difference between two groups (p?<?0.001). Hair As level has a median 1.01 (min: 0.06 and max: 25.71). There were no significant correlation between hair As levels and BMD measurements.

Conclusion: According to our observations, As exposure was associated with bone metabolism. Possible cause of osteopenia may be exposure to As. Further investigations are needed to estimate the relationship between As and bone metabolism.     

Bone mineral density at distal forearm in men over 40 years of age in Mae Chaem district,Chiang Mai Province,Thailand: a pilot study

Objective: To study the prevalence of bone mineral density (BMD) and osteoporosis in the distal forearm among Thai men over 40 years of age in Mae Chaem District, Chiang Mai Province, Thailand.

Methods: The subjects in this study were 194 Thai men, aged between 40 and 87 years who resided in Mae Chaem District, Chiang Mai Province, Thailand. Self-administered questionnaires were used for receiving the demographic characteristics information. BMD was measured by peripheral dual energy X-ray absorptiometry at the nondominant distal forearm in all men.

Results: The BMD was highest in the age-group 40–49 years and lowest in the age-group 70–87 years. The average T-score at the distal forearm was also highest in the age-group 40–49 years and lowest in the age-group 70–87 years. The BMD decreased as a function of age-group (p?p?p?>?.05). The percentage of osteopenia and osteoporosis are increased as a function of age-group in, while decreased in that of normal bone density.

Conclusions: We found the prevalence of osteoporosis in men who resided in Mae Chaem District, Chiang Mai Province, Thailand.     

Osteoporosis knowledge and attitudes: a cross-sectional study among college-age students

OBJECTIVE: The authors' purpose in this study was to investigate the influence of knowledge of osteoporosis, attitudes regarding osteoporosis, and knowledge of dietary calcium on dairy product intake in both male and female college-age students. PARTICIPANTS: The authors conducted this cross-sectional study on 911 men and women enrolled in 2 demographically similar universities. METHODS: A modified osteoporosis knowledge questionnaire assessed participant's general osteoporosis knowledge and perceived disease risk. RESULTS: The authors found that knowledge of osteoporosis and calcium did not significantly influence dairy product intake. Attitude regarding osteoporosis was a significant predictor of dairy product intake in men but was not significant for the women. CONCLUSIONS: The authors recommend development and implementation of educational programs designed to increase awareness of calcium-rich food sources as well as other risk factors of this crippling disease.     

Trunk stabilization with sling training in osteoporosis patients—a randomized clinical trial

Fractures due to osteoporosis are one of the principal causes of functional limitations, chronic pain, and greater morbidity in advanced age. In addition to bone risk factors for osteoporotic fractures include extraosseous causes such as falls or reduced neuromuscular capacity. Muscle and coordination exercises enhance the patients’ abilities in daily life and prevent falls. In view of recent conclusions drawn from competitive sports, which stress the significance of the muscles of the trunk in respect of reducing back pain and optimizing posture, we used sling exercises to determine whether osteoporosis patients benefit from it and whether it is more advantageous than traditional physiotherapy. Fifty patients were randomized into two groups. Group A received traditional physiotherapy, while group B was given sling exercises, in each case twice a week for a period of 3 months. The results of treatment (pre-post) were analyzed in terms of pain levels, mobility, trunk strength, and the shape of the back. After a further 3 months with no specific exercise treatment, we retested all patients in order to draw conclusions about the long-term effects of the two types of exercise. Forty-four patients (88 %) completed the study. Patients were assigned to small groups (a maximum of five patients in each group) and, thus, received individual attention and motivation. Positive training effects were achieved in both groups. Significantly better results as regards improvement of mobility and reduction of falls were registered in the sling exercise group.     

Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study

We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm(2); femoral BMD= 0.847 ± 0.117 g/cm(2)). TU induced a significant improvement of bone mass after 36 months (lumbar BMD=1.053 ± 0.145 g/cm(2); p < 0.002; femoral BMD=0.989 ± 0.109; p < 0.003 g/cm(2)) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r(2)?= 0.66, p < 0.0001) and femoral (r(2)?=0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middle-aged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.     

Impact of recreational physical activity on bone mineral density in middle-aged men

Physical activity is known to exert beneficial effects on general health status of young, adult and elderly populations. Exercise (aside from genetic, hormonal, nutritional and pathological factors) also influences bone mineral density (BMD). Unfortunately, the association between physical exercise and BMD in adult population is controversial. Our aim was to assess relations between recreational physical activity and BMD in middle-aged men. We performed densitometry and hormonal measurements (total testosterone, free testosterone, dehydroepiandrosterone sulfate, estradiol) in a homogenous group of 38 subjects. Among them, we distinguished 22 who had not engaged in any physical activity, and 16 who had recreationally exercised for about 10 years. Both groups did not differ in regard to hormonal status. Similarly, densitometry did not reveal any statistically significant differences in BMD between both groups of men. Upon our observation, we can hypothesize that recreational physical activity does not affect bone mineral density in middle-aged men.     

The effects of daily alendronate,daily calcitonin and alendronate every other day on bone mineral density in osteoporotic men

Objectives. Biphosphonates have been widely used in the treatment of osteoporosis, but there is not enough data on their use in men. The aim of this study is to investigate the effects of twelve months' treatment with daily 10 mg alendronate, every other day 10 mg alendronate and daily 200 IU calcitonin on bone mineral density (BMD) in men with osteoporosis.

Materials and methods. 46 men with osteoporosis were randomly allocated to three groups: 15 patients in the first group received daily 10 mg alendronate and calcium (1000 mg/day), 14 patients in the second group used every other day 10 mg alendronate and calcium and 17 patients in the third group were given intranasal salmon calcitonin and calcium. At the baseline, sixth and twelfth months, BMD was measured at lumbar spine (L_2–4), femoral neck and Ward's triangle zone by means of dual energy X-ray absorptiometry (LUNAR).

Results. In daily and every other day alendronate and calcitonin groups there was a significant increase in BMD at lumbar spine (p = 0.004, p = 0.001, p = 0.04), but no difference at the femoral neck (p > 0.05) at the end of twelve months. When the groups were compared with each other, no significant differences in BMD levels at lumbar spine, femoral neck and Ward's triangle were found (p > 0.05).