Cause Of Osteoporosis In Men Research Articles

Treatment of osteoporosis in hypogonadal men

About 3million men have been reported to have osteoporosis in Japan. One of known causes of osteoporosis in men is late-onset-hypogonadism. Androgen replacement therapy has been reporte to be effective in seveal literatures, however, patitiets should be excluded if prostate cancer is suspected. Addition of bisphosphpnate and active vitain D derivatives are recommended.

Osteoporosis in men: a review.

Osteoporosis and consequent fracture are not limited to postmenopausal women. There is increasing attention being paid to osteoporosis in older men. Men suffer osteoporotic fractures about 10 years later in life than women, but life expectancy is increasing faster in men than women. Thus, men are living long enough to fracture, and when they do the consequences are greater than in women, with men having about twice the 1-year fatality rate after hip fracture, compared to women. Men at high risk for fracture include those men who have already had a fragility fracture, men on oral glucocorticoids or those men being treated for prostate cancer with androgen deprivation therapy. Beyond these high risk men, there are many other risk factors and secondary causes of osteoporosis in men. Evaluation includes careful history and physical examination to reveal potential secondary causes, including many medications, a short list of laboratory tests, and bone mineral density testing by dual energy X-ray absorptiometry (DXA) of spine and hip. Recently, international organizations have advocated a single normative database for interpreting DXA testing in men and women. The consequences of this change need to be determined. There are several choices of therapy for osteoporosis in men, with most fracture reduction estimation based on studies in women.

Identification par l’analyse des facteurs cliniques de risque et la densitométrie osseuse des hommes à risque d’ostéoporose

Male osteoporosis is often secondary to other conditions. However the causes of osteoporosis in men are dramatically variable according to the authors. The aim of this observational multicenter study was to assess the main risk factors and causes for male patients with low bone mineral density (LBM). The study was performed in a cohort of rheumatologists who usually prescribe bone mineral density assessment according to HAS criteria (one or more criteria) for bone mineral density (BMD) measurement as defined by: (a): vertebral fracture; (b): non traumatic non vertebral fracture; (c): corticosteroid therapy; (d): hypogonadism or GnRH agonist therapy; (e): endocrine disorders; (f): osteogenesis imperfecta (OI). BMD was measured by dual photon absorptiometry (DXA) at lumbar spine, femoral or total neck sites. Osteoporosis was defined as a T-score value less or equal to 2.5 at one of those region of interest (ROI); LBM as a T-score value between -1 and -2.5. A total of 431 rheumatologists included 1198 male patients (66.6 ± 12.2 years). According to DXA results, 888 patients (74.1 %) had osteoporosis and 231 (19.3 %) had osteopenia. BMD was considered as normal for 79 patients (6.6 %). A total of 1146 patients (95.7 %) satisfied to the criteria of reimbursement of DXA measurement. Six hundred and eighty-six patients (57.3 %) had suffered from vertebral fractures and 349 patients (29.2 %) from non vertebral fractures. Corticosteroids had been prescribed in 28.7 % of patients and 6.6 % were treated with GnRH agonists for prostate cancer. Hypogonadism was diagnosed in 27 %. Five patients suffered from OI. Other risk factors were detected: alcoholism and smoking in 28.1 % and 42.9 % respectively; rheumatoid arthritis or spondylarthropathy in 12.5 % of patients; chronic pulmonary disorders in 16.1 %. By contrast endocrinopathies were rare (2.5 %). Several risk factors were more frequently encountered for patients with osteoporosis as compared with osteopenia, i.e., smoking, alcohol abuse, low calcium intake, vitamin D insufficiency and maternal history of hip fracture. A diagnosis of osteoporosis (BMD ≤ 2.5) was established by rheumatologists in 74.1 % of patients with clinical risk factors: LBM was found in 93.4 %. In 95.7 % the criteria for reimbursement of DXA measurement were satisfied. DXA is useful in male patients with classical risk factors of osteoporosis to confirm the diagnosis of the disease and start a treatment.

Androgens and osteoporosis

The review is timely given recent advances regarding mechanisms of androgen action on bone cells and in humans. Osteoporosis in men is an important public health problem. An improved understanding of the role of androgens in the pathophysiology of bone loss will lead to new treatments. Androgen receptors are present in most bone cells. Testosterone acts on bone both directly via the androgen receptor and indirectly, following aromatization, via the oestrogen receptor. During skeletal modelling, ERalpha is critical for longitudinal bone growth. For periosteal growth and bone expansion, androgen receptor activation has a positive effect, whereas ERalpha activation is inhibitory. During skeletal remodelling, both receptor pathways generate similar and additive effects on bone.Androgen deficiency is a common secondary cause of osteoporosis in men and should be treated with testosterone, particularly in symptomatic men. However, lack of efficacy data for testosterone in osteoporosis means it is less useful as a first-line treatment in men with age-related declines in testosterone and osteoporosis, when other agents such as bisphosphonates and parathyroid hormone are effective. Randomized, placebo-controlled trials of testosterone therapy in men with age-related declines in testosterone and osteoporosis are needed, and should carefully evaluate potential risks, as well as its efficacy in reducing fractures and other health benefits.

Osteoporosis in men: Prevalence and investigation

In the past, osteoporosis was thought to affect only women; however, in the last decade it has become apparent that osteoporosis is common in men, particularly elderly men. Osteoporosis affects as many as 2 million men in the United States. Osteoporosis most commonly affects the hip and the lumbar vertebrae, but other bones, such as the radius, tibia, and ribs, may also fracture. The main feature of the etiology of the disease is that low bone mineral density results in increased susceptibility to bone fracture. The World Health Organization has defined osteoporosis as a bone mineral density T-score value >2.5 SDs below the mean observed in young adult women. Although the validity of this score for evaluating men has been questioned and it is not clear whether a male or female reference database should be used, it is nonetheless often used in this way. The disease affects men differently than women in a number of respects. It manifests itself later in life in men than in women, probably because men initially have greater bone mass. Mortality and morbidity associated with hip fractures are high in all elderly individuals, but they are substantially higher in men than in women. Unlike in women, there is an underlying cause for the osteoporosis in almost half of affected men. Thus, for elderly men, a complete history and physical examination may reveal some remediable conditions; treating these may stop further progression of the disease and prevent further morbidity or mortality. Corticosteroid therapy for arthritis or asthma is a common cause of osteoporosis in elderly men. Hypogonadism is a recognized cause of osteoporosis in men treated for carcinoma of the prostate with androgen withdrawal therapy; treatments to modify the effects of these agents on bone are available. Consumption of large amounts of alcohol will eventually result in osteoporosis in some elderly men. Moreover, alcohol can predispose confused elderly patients to falls and to fracture bones that are already osteoporotic. Hyperthyroidism is associated with a reduction in bone mineral density and an increased likelihood of bony fracture. A careful search for undiagnosed hyperthyroidism in elderly osteoporotic men may prove worthwhile. Vitamin D deficiency is common among older men and could contribute to an increase in fractures. Routine analyses of blood and biochemistry should be carried out in any older male patient with newly diagnosed osteoporosis. Dual x-ray energy absorptiometry should be performed on every new patient with newly diagnosed osteoporosis.

Therapy Insight: osteoporosis during hormone therapy for prostate cancer

The intended therapeutic effect of gonadotropin-releasing-hormone (GnRH) agonists is hypogonadism, which is a leading cause of osteoporosis in men. Observations are consistent with this effect: GnRH agonists decrease bone mineral density and increase fracture risk in men with prostate cancer. Estrogens play a central role in homeostasis of the normal male skeleton and evidence suggests that estrogen deficiency is primarily responsible for the adverse skeletal effects of GnRH agonists. The mechanism of treatment-related bone loss involves acceleration of physiologic bone turnover. In small, randomized, controlled trials, bisphosphonates (pamidronate, zoledronic acid) and selective estrogen-receptor modulators (raloxifene, toremifene) increased bone mineral density in GnRH-agonist-treated men. Two ongoing large, randomized, placebo-controlled studies will prospectively define fracture outcomes in men with prostate cancer and assess the efficacy of novel pharmacologic interventions (AMG 162, toremifene) in GnRH-agonist-treated men.

Idiopathic or Hypogonadal Osteoporosis in Men

Osteoporosis is being recognized increasingly in men, and represents a substantial public health problem. As the male population ages and lives longer, the incidence of osteoporotic fractures is expected to increase. The current lifetime risk for a fragility fracture is approximately 27% in men aged 50 years or more, and will increase further over the next 20 years. A major problem with osteoporosis in men is that it continues to be unrecognized, and the majority of men with fragility fractures due to osteoporosis are not being treated. A higher level of awareness is required amongst both general practitioners and the general public that osteoporosis is a treatable condition that can affect men. Secondary causes for osteoporosis are more common in men than in women, and require rigorous exclusion and treatment. Undiagnosed clinical hypogonadism is a common cause of osteoporosis in men, and is readily treatable. The cause of primary osteoporosis in men is unknown, but it results in an osteoblast defect. Genetic factors are likely to be important. In some but not all men, relative estrogen deficiency contributes to rapid rates of age-related bone loss and fractures. An adequate calcium intake, regular weight-bearing exercise, and normal vitamin D status are all very important, particularly with increasing age. The role of testosterone in treating eugonadal men with osteoporosis is currently unclear, and larger prospective studies will be required to carefully evaluate the benefits and risks of therapy. First-line treatment of osteoporosis in hypogonadal or eugonadal men is with bisphosphonates. Alendronate increases bone density and reduces vertebral fractures measured using a semiquantitative method in eugonadal or hypogonadal men with osteoporosis. In the near future, it is likely that subcutaneous human parathyroid hormone (1-34) or teriparatide will also be available as an important new anabolic treatment for men with osteoporosis. Teriparatide treatment also increases bone density in men. Selective estrogen receptor modulating drugs require further evaluation in men, but would appear to theoretically benefit men, especially those with low estradiol levels. In the future, selective androgen receptor modulating drugs may be useful in the prevention and treatment of osteoporosis, and in increasing lean body mass in men, without having adverse effects on prostate and breast tissue.

Mutational and polymorphic analysis of the estradiol receptor-alpha gene in men with symptomatic vertebral fractures.

In view of the importance of estrogens in the maintenance of the skeleton in men, we have carried out mutational analysis of all the exons of the estrogen-receptor-alpha (ER-alpha) gene in 64 men (36 patients with symptomatic vertebral crush fractures and 28 control subjects). Initial screening of the ER-alpha gene, carried out by single-strand conformation polymorphism analysis followed by sequencing, showed conservative mutations in exon 4 which resulted in a single base substitutions producing GGG-->GGC transition in codon 274. We also carried out polymorphic analysis of the ER-alpha gene at the PvuII restriction site in 82 men with a range of bone density measurements (53 with symptomatic vertebral fractures and 29 controls). The frequencies of PP, Pp, and pp genotypes were 20.7%, 48.8%, and 30.5%, respectively. The distribution of the alleles was similar in the patients with symptomatic vertebral crush fractures and male control subjects. There was no association between ER-alpha genotypes and bone mineral density or arthropometric parameters. This relatively small study suggests that mutations in the ER-alpha gene are unlikely to be a common cause of osteoporosis in men with vertebral fractures. Furthermore, polymorphic variation of the ER-alpha gene appears to have little effect on the pathogenesis of osteoporosis in men.

Secondary causes of osteoporosis in men.

Important underlying causes of osteoporotic fracture in men include glucocorticoid therapy, low body weight, and reduced physical activity. Tobacco and alcohol use have been consistently identified as risk factors for vertebral fracture but there is less evidence that they contribute to hip fracture. Clinically overt hypogonadism is a strong risk factor for osteoporosis in men; however, the role of more subtle subclinical changes, as defined by biochemical criteria, remains to be established. The high comorbidity associated with osteoporosis, particularly in elderly men, contributes to fracture risk both through effects on bone mass and risk of falling. The management of osteoporosis in men includes diagnosis of and, where possible, correction of underlying contributory causes. Evidence from recent randomized controlled trials indicates that bisphosphonates are effective in the prevention of glucocorticoid-induced osteoporosis in men but the optimal criteria for selection of individuals for treatment requires further study.

Bone loss associated with the use of LHRH agonists in prostate cancer.

Hypogonadism is a recognised cause of osteoporosis in men. When patients with advanced prostate cancer are treated with luteinising hormone releasing hormone (LHRH) agonist analogues their circulating testosterone levels decline and these patients may develop fractures.We have undertaken a cross-sectional study on a cohort of patients treated with goserelin (n=41) and compared their bone density and bone turnover with patients with prostate cancer not on goserelin and elderly patients living in the community.There was no difference in bone density between the patients on treatment and those living in the community and there was a similar incidence of osteoporosis (50 and 42%, respectively). The bone marker measurements were higher in the treated patients: urine N-telopeptide (NTX) 80.1 (9) (mean (s.e.)) BCE/mmol, compared to 30.1 (2.9), P<0.001 in elderly patients; and bone alkaline phosphatase 41.9 (6.1) u/l in treated patients and 20.7 (1.5) in untreated prostate cancer patients, P<0.002. Patients on treatment with radionuclide scan evidence of metastases did not have higher bone marker values than those with negative scans.As increased bone turnover and low bone density are associated with enhanced risk of osteoporotic fractures, we suggest that patients on LHRH agonist analogues should receive advice and possibly anti-bone resorptive treatment with bisphosphonates to prevent further bone loss and fractures.Prostate Cancer and Prostatic Diseases (2001) 4, 161-166.

Osteoporosis in men

This article highlights the relative lack of knowledge and current research on osteoporosis in men. The annual cost of osteoporotic fracture in the UK is in excess of £940 million, of which 23% is due to fractures in men. Twenty per cent of symptomatic vertebral fractures and 30% of hip fractures occur in men. Bone density in men is influenced by genetic, hormonal, mechanical and nutritional factors. There is no well-established treatment for idiopathic osteoporosis in men, but options include bisphosphonates and testosterone supplementation. Further work is required to clarify the causes of osteoporosis in men and to develop criteria for the diagnosis of male osteoporosis.

Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis.

Previous studies suggest that low bone mass is a complication of alcoholic liver disease. Nevertheless, little is known about bone mass and bone metabolism in viral cirrhosis. To evaluate the prevalence and magnitude of hepatic osteopenia in these patients, bone remodeling status, and its relationship with the severity of liver disease and serum levels of insulin-like growth factor I (IGF-I), we studied 32 consecutive patients with viral cirrhosis and no history of alcohol intake. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN), and the values were expressed as the z score. Bone metabolism markers and hormone profiles were measured. Patients with viral cirrhosis showed reduced BMD in all sites (LS: -1.27 +/- 1.06, P < .001; FN: -0.48 +/- 0.96; P < .01). Of the 32 patients, 53% met the diagnostic criteria for osteoporosis. In patients, urine deoxypyridinoline (D-Pyr) as a marker of bone resorption and serum bone alkaline phosphatase (b-AP) as a marker of bone formation were significantly higher than in control subjects (P < .001 and P < .01, respectively). Serum IGF-I was lower than in control subjects (P < .001), and significant differences were also found between patients with and without osteoporosis (P < .05). BMD in LS correlated with severity of the disease, with serum levels of IGF-I, and with urine D-Pyr. Our findings show that viral cirrhosis is a major cause of osteoporosis in men, and that low serum IGF-I levels seem to play a role in the bone mass loss in these patients. The biochemical markers of bone remodeling suggest high-turnover osteoporosis in patients with viral cirrhosis.

Endocrine disorders and osteoporosis

Endocrine disorders constitute the most frequent cause of secondary osteoporosis in men and women. Because endocrine diseases are common (e.g., diabetes mellitus, hyperparathyroidism, and hyperthyroidism), they should be considered in the differential diagnosis and management of osteopenia. The pathogenesis of hormone-induced bone loss involves several components of the bone remodeling cycle and in many cases is not fully elucidated. Identifying an underlying cause and correcting hypo- or hyperfunction of an endocrine gland, however, can often lead to an increase in bone mineral density. This review focuses on recent studies on hormonal disorders that affect the skeleton. In particular, diabetes mellitus, hyperparathyroidism, and hyperthyroidism are considered within the context of both accelerated bone loss and fracture risk.

Aetiology and presenting symptoms in male osteoporosis.

In order to analyse the clinical characteristics and the principal causes of osteoporosis in men, 81 osteoporotic males from an out-patient rheumatology department were studied. Bone mass assessment, automated biochemical profile and biochemical markers of bone turnover were performed in all patients, and hormonal measurements were taken when a specific aetiology was not readily apparent. Sixty-three men (78%) had secondary osteoporosis and 18 (22%) primary osteoporosis. Secondary causes of osteoporosis included hypogonadism (12 patients), corticosteroid therapy (10 patients) and alcoholism (10 patients); the remaining patients had various causes of osteoporosis. Eighteen patients had primary osteoporosis, eight of them with associated hypercalciuria. Normocalciuric patients showed lower 25-hydroxyvitamin D and 1-25-hydroxyvitamin D levels than the control group, whereas hypercalciuric patients had lower parathyroid hormone and renal threshold for phosphate excretion. In 69 patients (85%), back pain was the chief complaint. Forty-five of these 69 patients (65%) had chronic back pain and 24 (35%) had subacute episodes. Fifty per cent of the patients with chronic back pain had vertebral fractures. Both patients with and without chronic back pain were found to have a similar number of vertebral fractures. In conclusion, male osteoporosis is frequently associated with major risk factors. Patients with primary osteoporosis may have associated hypercalciuria or decreased vitamin D levels. However, not all the patients for whom back pain was the chief complaint were found to have vertebral fractures.

Chronic alcoholism. Frequently overlooked cause of osteoporosis in men

A radiographic survey was made of 96 fully ambulatory male patients who were admitted to a rehabilitation center for patients with chronic alcoholism in an attempt to estimate the incidence of skeletal demineralization in these patients. The age of the patients ranged from 24 to 62 years. Forty-five of the 96 male patients, or 47 percent of this group, showed radiographic evidence of extensive bone loss. Fourteen or 31 percent of these 45 patients with bone loss were relatively young (age 31 to 45 years), and half of this group of 14 patients were less than 40 years old. The majority of the 45 patients with radiographic evidence of osteoporosis, namely, 31 patients or 69 percent, were older and ranged in age from 46 to 62 years. One third of the patients in this group were less than 50 years old. The radiographic survey of the 96 patients indicates the high incidence of extensive bone loss, most likely osteoporosis, in relatively young and middle-aged ambulatory men with chronic alcoholism. In 12 additional patients with chronic alcoholism who were observed in the Metabolic Research Ward, and who were not part of this survey, bone biopsy specimens confirmed the radiographic diagnosis of osteoporosis.