Osteoporosis in Elderly Men

Authors: Neil Baum, MD Case Presentation A 66-year-old male had a routine physical examination. He had a moderately enlarged benign prostate gland. The prostate-specific antigen (PSA) was 7.7, and the ratio of free/total PSA was 9% (normal > 25%). A prostate biopsy revealed multiple cores of adenocarcinoma of the prostate, Gleason score 3 + 4. He was treated with I-125 brachytherapy plus 20 Gy of external beam therapy to the periprostatic tissue, and the PSA nadir was 0.7 ng/mL 6 months after the radiation therapy. However, 6 months later the PSA increased to2.7, and repeat PSA testing demonstrated progressive increase in the PSA. A ProstaScint scan demonstrated recurrence in the prostate. He was offered salvage radical prostatectomy, cryotherapy, or total androgen ablation consisting of luteinizing hormone-releasing hormone (LHRH) agonist and anti-androgen therapy. He opted for the latter, and the PSA decreased to < 0.1 ng/mL. He noted loss of height, lethargy, and falling asleep after meals. A bone mineral density (BMD) dual energy x-ray absorptiometry (DEXA) scan was obtained, which revealed that the patients T-scores were: spine = -2.2 and hip = -2.5 (Figure). Radiographic studies revealed a compression fracture at T-10, which confirmed the diagnosis of osteoporosis. Discussion The definition of osteoporosis for women is centered on the level of bone mass, measured as BMD for diagnostic purposes. Two thresholds of BMD have been defined by the World Health Organization on the basis of the relationship of fracture risk to BMD. The first threshold defines the majority of individuals who will sustain a fracture in the future (osteoporosis), and the second is a higher threshold more appropriate for the prevention of bone loss (low bone mass or osteopenia). Osteoporosis denotes a value for BMD that is -2.5 standard deviations or more below the young adult mean value (T-score less than -2.2). Low bone mass means a T-score that lies between -1 and -2. The risk of bone fracture increasees twofold for each standard deviation decrease in BMD. Suitable diagnostic cut-off values for men are not as well defined. A similar cut-off for BMD that is used in women can also be used for the diagnosis of osteoporosis and osteopenia in men.

The patient described represents a case of secondary osteoporosis, which is commonly seen in men treated with androgen ablation for prostate cancer. Secondary osteoporosis can be caused by medical conditions (inflammatory bowel disease, malabsorbtion), prescription medication (corticosteroids, thyroxine, anticonvulsants), or an unhealthy lifestyle (inactivity, tobacco, and excessive alcohol consumption). Nearly half of all men with osteoporosis have no known cause for their disease. Osteoporosis in men can be a major health problem. In 2004, there were 10 million Americans with osteoporosis (8 million women and 2 million men) and 18 million with low bone mass.1 Because of the predicted growth in the number of elderly persons in this country, the number of men with osteoporosis is expected to increase dramatically.2 Yet, despite the large number of men affected, osteoporosis in men remains underdiagnosed, underreported, and inadequately treated. Although osteoporosis is less common in men than in women, it is estimated that one-fifth to one-third of all hip fractures occur in men. Symptomatic vertebral fractures occur about half as often in men as they do in women. Seventeen percent of men who reach age 90 have had a hip fracture in their lifetime, and hip fractures can be catastrophic in older men who are at increased risk of chronic physical disability and even death. In fact, men are much more likely than women to die or experience chronic disability after a hip fracture. Twenty-four percent of people die in the year following a hip fracture.

This disease causes nearly 1.5 million fractures annually and costs this country nearly $18 billion each year.3 Osteoporosis is less common in men than in women for several reasons: men have larger skeletons, their bone loss starts later in life and progresses more slowly, and they do not experience the rapid bone loss that affects women when their estrogen production quickly drops as a result of menopause. Despite these differences, men can be at high risk for this disease. The best long-term information available suggests that at age 60, Caucasian men have a 25% chance of sustaining an osteoporotic fracture. Men can experience a marked loss of bone as they age, and this decline in bone mass is an important contributor to the development of osteoporosis. There are several reasons for this loss of bone. Declining testosterone levels may cause bone loss that is similar to the bone loss that occurs in women at the time of menopause and estrogen deficiency. In addition, estrogen

may play a critical role in bone health in men. Changes in estrogen levels with age may be as important, if not more important, as those changes in testosterone. Moreover, the amount of time devoted to exercising generally declines with age, and dietary calcium intake, as well as the ability to absorb calcium, tends to fall. Finally, there may be age-related changes in the basic metabolic activity in bone that contribute to bone loss.4 The risk of fracture posed by age-related bone loss is increased considerably by a tendency for the elderly to fall more often. There are many factors that increase a mans risk of developing osteoporosis. Approximately 50-60% of men with osteoporosis have disorders or conditions that can produce bone loss, including hypogonadism (low production of testosterone), hyperparathyroidism, intestinal disorders, malignancies, steroid therapy (eg, chronic prednisone treatment), and immobilization. Hypogonadism has recently been of particular interest, since it can be present with few or no symptoms or insidious symptoms, such as loss of energy, lethargy, decreased libido, and falling asleep after meals. Additional risk factors for low bone density include unhealthy lifestyle behaviors, such as smoking, alcohol abuse, chronic inactivity, and low body weight (especially if further weight loss occurs). Of interest is the fact that despite extensive testing, no obvious cause has been found in a large number of men who develop fractures or have low BMD. When osteoporosis develops in the absence of recognized risk factors, the condition is known as idiopathic osteoporosis. The evaluation of osteoporosis in men is similar to that in women. Fractures that occur in the absence of trauma should always raise the suspicion of osteoporosis, and the possibility of osteoporosis should be considered in men who have any of the risk factors mentioned above. Bone density measurement of the spine, hip, or other sites such as the distal third of the radius can provide valuable information concerning bone mineral content, bone strength, and the risk of future fractures. The most-used technique to diagnose osteoporosis/osteopenia is the DEXA at axial and appendicular sites. For diagnostic purposes alone, DEXA at the hip is the preferred siteparticularly in elderly menbecause of its higher predictive value for fracture risk. The spine is not as suitable a site for diagnosis in the elderly because of the high prevalence of arthritis, but it is the preferred site for assessing the response to treatment. If osteoporosis is found, careful evaluation should include a search for underlying factors that contribute to bone loss (medical conditions, dietary habits, tobacco use, alcohol intake, immobilization, etc).

Blood and urine tests such as an increase in N-telopeptide of type I collagen (NTx), a marker of bone resorption seen in men after receiving gonadotropin-releasing hormone (GnRH) agonist therapy, may identify many of the secondary causes of osteoporosis. Additionally, a thorough medical evaluation may identify additional med ical conditions or medications that may play a role in poor balance and an increased risk of falling. The treatment of osteoporosis in men consists of identifying and treating specific causes of bone loss and maintaining a balanced diet with an adequate intake of calcium (1000 mg/day in younger men and 1200-1500 mg/day in men over age 65 years) and vitamin D (400-800 IU/day). An exercise program that includes weight-bearing activities should be insti tuted. An integral part of osteoporosis prevention and treatment should also include a recommendation for an appropriate exercise or physical therapy program. Weight-bearing exercise and resistance training are especially helpful. If testosterone deficiency is found by a blood test documenting hypoandrogenism, testosterone replacement therapy should be consid ered. This can be administered by either an injection of testosterone enanthate, transdermal patches, or topical gels. Of course, testosterone replacement ther apy is contraindicated in patients with prostate cancer. Other treatments for use in men include calci tonin, bisphosphonates (eg, alendronate 10 mg/day or one 70-mg tablet/week, risedronate 5 mg/day or one 35-mg tablet/week, human parathyroid hor mone, teriparatide (one injection, 20 mcg/day for 24 mo), and others such as ibandronate sodium. Preventing bone loss and fractures is of primary importance. Where possible, risk factors such as smoking and excessive alcohol intake should be avoided, a balanced diet replete in calcium and vitamin D should be a priority, and proper exercise, particularly weight-bearing exercises, should be a regular part of weekly activities. Finally, the prevention of falls is very important, and common household hazards (such as slippery floors and unlit stairways) and medications or drugs that dull the senses and produce drowsiness should be avoided. As we learn more from research concerning the biology of bone, we will be able to develop new means to diagnose, prevent, and treat osteoporosis. Finally, we need to educate men that osteoporosis is not an inevitable consequence of aging. They need to know that it can be prevented by proper diet, exercise, and use of medication when necessary. Outcome of the Case Patient The patient was started on an exercise program that included weight-bearing exercise,

supplemental calcium and vitamin D, and a daily teriparatide injection 20 mcg/day into the subcutaneous tissue. After 6 months, a repeat DEXA scan demonstrated a 5% improvement in both the lumbar spine and femoral neck BMD. The patients serum PSA level remains at < 0.1 ng/mL, and he is asymptomatic from the prostate cancer. Dr. Baum is a Clinical Associate Professor of Urology, Tulane Medical School, New Orleans, LA. Acknowledgment The author would like to thank Dr. Mario McNally, an endocrinologist, for reviewing this manuscript. References 1. Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 20052025. J Bone Miner Res 2007;22:465-475. 2. Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: A worldwide projection.Osteoporos Int 1992;2:285-289. 3. U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. U.S. Department of Health and Human Services, Office of the Surgeon General, 2004. 4. Orwoll ES, Klein RF. Osteoporosis in men. Endocr Rev 1995;16:87-116.