Men's Osteoporosis Support GroupMale osteoporosis Endocr Rev. 2008 May 1. [Epub ahead of print], Osteoporosis in Men. Khosla S, Amin S, Orwoll E. PMID: 18451258. This very extensive review of osteoporosis in men is available free as a PDF file. There are 81 pages, including the references and tables, so there will be much to learn about male osteoporosis if you care to read the entire paper. I am going to just highlight some of the points that I find significant in the summary below. But I hope you will take the time to read the entire article.
Introduction. Osteoporosis is not confined to women only. In fact: 1. One in eight men over age 50 will have an osteoporosis-related fracture in their lifetime. 2. Almost 30% of hip fractures are in men. 3. Men have greater morbidity and mortality than women after a fracture.
Epidemiology. 1. Kanis and Johneel estimated that 9 million new osteoporotic fractures occurred worldwide in the year 2000, of which 39% were in men. 2. Women fall more frequently than men which may account for the lower incidence of fractures in older men. As well women fracture 2.2 times more than men do when they do fall after age 65. 3. Hip fractures: a. Most occur in men after age 75 and cause the most morbidity and mortality. b. Scandinavian and North American men have the highest incidence of hip fracture, while blacks and Asians have the lowest incidence. c. Countries with the greatest economic prosperity have the highest hip fracture rate. d. Men are twice as likely to die in hospital after a fracture than are women. e. In men aged 60-69, the decrease in life expectancy after a hip fracture is 11.5 years compared to men age 70-79. Yet men are less likely to be investigated or treated for osteoporosis after hip fracture. f. In one study, only 7% of men compared to 31% of women were given osteoporosis therapy at hospital discharge for hip fracture. At 1 to 5 years of follow-up, 27% of men received osteoporosis treatment in contrast to 71% of women. And 67% of the men receiving treatment were only on calcium and vitamin D. 4. Vertebral fracture. a. Vertebral fractures are often asymptomatic, but studies show they are prevalent in men and occur more with increasing age and decreasing bone density as measured at the total hip. b. Vertebral fractures are predictive of subsequent fractures, and also predict mortality in men during the forthcoming decade. c. A vertebral deformity in men is also associated with lower energy, poorer sleep, pain, immobility and social isolation. 5. Note on the reference to Figure 2 and the study by Schuit SC and others in Bone 2004 Jan;34(1):195-202. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. PMID: 14751578. Here is a quote from the abstract: "Only 44% of all non-vertebral fractures occurred in women with a T-score below -2.5; in men, this percentage was even lower (21%). Thus, there is a clear need for the development of more sensitive risk assessment tools, using not only BMD, but also other clinical predictors of fractures." Check figure 2 for yourself and you will see that for hip fractures in men, over 60% occurred in those who were either osteopenic or with normal bone mineral density (BMD). Or, put another way, men are at greater risk for a hip fracture without osteoporosis (as currently defined) than with it. This means the definition of osteoporosis as a T-score of -2.5 S.D. below the normal is questionable regarding fracture risk.
Pathogenesis of bone loss in men 1. Age-related bone loss. a. Bone contains the dense outer cortical layer and the inner woven, spongy trabecular layers. DXA (dual-energy X-ray absorptiometry) tells us nothing of the specifics of the cortical and trabecular bone. Fortunately QCT (quantitative computed tomography) can give us more information about changes to cortical and trabecular bone with aging. With QCT it was shown: 1). Spinal (mainly trabecular) bone volumetric BMD (vBMD) has large decreases with age. This is similar to what happens in the trabecular bone of the femur neck, distal radius and distal tibia. 2). Cortical vBMD remains relatively stable until about age 65-70, when it decreases thereafter. 2. Role of sex steroids. a. In men it was previously thought that sex hormones were not a major cause of age-related bone loss. However, it is now known that the bioavailable testosterone and estradiol are the important components to measure, not just total steroids. See Table 2 regarding all changes in male serum sex steroids and gonadotropins over life. b. It has been thought that serum testosterone was the primary determinant of male BMD, however, there is evidence that BMD correlates better with serum estradiol levels, particularly bioavailable estradiol levels. The authors, however, state that correlation does not prove causality. c. Another study compared sex steroid levels to yearly forearm BMD to try to find the important sex steroid regarding loss of BMD. This study found that below 40 pmol/L, bioavailable estradiol levels were clearly associated with the rate of bone loss in men. It appears that the important factor for BMD in men is that their bioavailable serum estradiol is at or above the normal median range. d. Be sure to read about the study on page 22 and 23 regarding the importance of estradiol or testosterone, it is a fascinating study. Basically the authors used biochemical markers of bone formation and resorption when using a carefully controlled method that tested the effectiveness of testosterone alone, estradiol alone, both hormones together, or no hormones. This study found that estrogen accounted for more than 70% of the total effect of sex steroids on bone resorption while testosterone could only account for about 30% of the effect. e. Several studies have also shown the importance of low serum estradiol levels regarding increased fracture risk for men. If both estradiol and estrogen levels were low, this also increased the fracture risk. There is no mention of approved estradiol products if male estrogen levels are decreased. If there are any such products, I'm not aware of them. It does appear, however, that some men probably do need additional estradiol to improve their BMD. 3. Other hormonal factors. a. Decreased vitamin D levels and increased serum parathyroid hormone (PTH) probably account for male BMD loss with aging. Aging is also associated with decreased growth hormone secrection. b. DHEA studies have been unclear regarding BMD. 4. Other factors. a. Nutritional factors, such as inadequate calcium or protein intake, my accelerate the loss of BMD. Also the loss of muscle mass and reduced physical activity with aging may be very important.
Idiopathic osteoporosis (IP) in men 1. IP is defined as the development of osteoporosis and fractures in a male before age 60. 2. Up to 10% of men with IP may also have hypercalciuria. 3. In the small group of men studied so far with IP, there is an increase in serum SHBG (serum hormone binding globulin) levels which leads to decreased free estradiol and androgen indices. Also, serum bioavailable estradiol levels may be low even though testosterone levels are normal. 4. There may also be a reduction in IGF-I levels that may be genetic.
Secondary osteoporosis in men 1. Secondary osteoporosis via alcohol abuse, glucocorticoid excess (mainly from chronic therapy), and hypogonadism account for 40% of male osteoporosis. 2. See table 1 for a complete list of primary and secondary causes of osteoporosis in men.
Diagnostic criteria 1. Who should be tested for osteoporosis? Those with factors associated with low BMD and fractures. a. Measures of BMD. 1) BMD is highly predictive of fracture risk in men necessitating BMD measurement when men have conditions associated with fracture risk and low BMD. In this higher risk group some include all men over age 70 and others, for cost-effectiveness, include only those over age 80, as well as those older than 65 who have had a previous fracture. 2) DXA is the first choice to measure BMD, with low DXA related to increased fracture risk in men. Pharmacological therapies appear effective in men found to have low BMD via DXA. 3) Ultrasound findings of low BMD are associated with increased fracture risk. But ultrasound is not effective in determining who should have pharmacological therapy or DXA. b. Laboratory evaluation. 1) Lab studies diagnostic yield is unknown. But low BMD is considered important in deciding to determine the cause of the low BMD. Approximately 20% of men may have osteomalacia which differs significantly from osteoporosis. 2) Routine lab tests should include serum creatinine, calcium, phosphorus, alkaline phosphatase, liver function tests, and a complete blood count. Additionally vitamin D levels should be determined. If these tests are inconclusive, 24-hour urine cortisol and immunological markers of sprue may be indicated.
Treatment 1. Bisphosphonates. a. Several trials show increased BMD and are suggestive or reduced fracture risk for alendronate (Fosamax) and risedronate (Actonel). b. BMD increases in men are as great in those with low free testosterone levels as those with normal levels, suggesting bisphosphonates are effective in men with hypogonadism. c. Bisphosphonates are also effective in men with secondary causes of osteoporosis. d. Although there are no current trials involving men using ibandronate (Boniva) and zoledronate (Reclast and Zometa), there is no reason to suspect they would not be as effective in men as they are in women. e. Bisphosphonates have been shown to be effective at preventing loss of BMD during androgen deprivation therapy for prostate cancer. Reduction in fracture risk has not yet been shown. 2. Parathyroid hormone (Teriparatide). a. This therapy has been shown to increase BMD in men with the thought that it should be as effective in fracture prevention in men as in women. b. Simultaneous therapy with bisphosphonates appears to blunt the effects of parathyroid hormone in men. 3. Calcitonin. There is little data to demonstrate a strong correlation between using calcitonin and either fracture or BMD benefits, and some small studies have been suggestive of this. 4. Thiazide diuretics. a. In case-controlled trials thiazides reduced the rate of loss of calcaneal bone density by 40% and the relative rate of hip fracture was halved by exposure of more than 6 years. b. This doesn't appear to be a primary treatment option, but would be the diuretic of choice in men with osteoporosis. 5. Strontium ranelate appears to be effective to increase bone formation and reduce bone resorption and fracture risk in women, but no studies have been published regarding men. 5. Sex steroid therapy. a. Although estrogen should be effective to increase BMD in men, no studies have been done to show this because of the problem with side effects such as gynecomastia. b. In adult hypogonadal men, testosterone therapy positively affects bone mass in most groups, with one study showing >20% increased BMD in the first year. c. These positive results don't appear to cover all groups, such as those with Kleinfelter's syndrome, who have variable results concerning BMD with testosterone therapy. d. Some benefits may also be due to increased muscle strength and lean body mass, which correlate with bone strength and reduced fall rates. e. There are many unresolved issues regarding testosterone therapy, especially for male andropause, but for many other areas, too. The authors present several which you can read if you want. 6. Calcium and vitamin D. a. Low vitamin D in older men has been linked to increased falls. b. No BMD or fracture benefit was found in men who were already well nourished when calcium and vitamin D was supplemented. Additionally no relation to the fracture rate was noted in the Health Professionals Follow-up Study for dietary calcium intake. c. Other studies have shown improvements in bone density in older men supplemented with calcium and vitamin D, so the studies show mixed results. In spite of this, authorities are recommending 1000 IU of vitamin D per day and 1200 mg/day of calcium for adults. 7. Exercise appears to benefit older individuals in that it increases strength and reduces falls which could lead to fracture. There are no specific exercise prescriptions that have been confirmed to be effective in men. Yet fracture rates are lower in men who exercise modestly.
Unresolved issues concerning osteoporosis in men 1. Whether male or female reference ranges should be used to define male osteoporosis T-scores. 2. With this information, just how prevalent is male osteoporosis? 3. Further understanding of hte hormonal and non-hormonal factors causing age-related bone loss in men. 4. Clarification of the causes of young male idiopathic osteoporosis. 5. Cost effectiveness of various lab tests for evaluating male osteoporosis. 6. The utility of measuring serum estradiol levels using standardized mass spectroscopy assays when evaluating male osteoporosis. 7. The risks/benefits of testosterone treatment of aging men who have declining bioavailable testosterone levels. 8. Studies with pharmacologic agents directly assessing fracture risk reduction in men rather than relying on inferences from studies in women.
Editor's comments: This is a nice review of the state of knowledge regarding men's osteoporosis in 2008. Not only is the review itself helpful, but all the references listed provide additional sources of information for those willing to check them out.
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