Commentary by Carrie Mahowald MD
Case: GS, a 65 year old man with only a history of severe OA, is seen in pre-op clinic for medical clearance before his hip replacement. On his pre-op x-ray, an incidental finding of a lumbar vertebral compression fracture is noted. After his hip replacement, how would you work him up for osteoporosis?
Osteoporosis, defined as low bone mass and the deterioration of bone micro-architecture which leads to the compromise of bone strength and the increased risk of fracture, is the most common bone disease in humans. Osteoporosis affects millions of people and the risk increases with increasing age causing significant mortality and morbidity including chronic pain, disability and death. Osteoporosis in men is less common than in women and therefore, unfortunately often overlooked. Two million men over age 65 have osteoporosis. Of all hip fractures, 25-30% occur in men. Osteoporosis, however, presents differently in men than in women. First, it manifests later in life (>75 years of age compared to >60-65 years in women). This is partly because men initially have a greater bone mass, and partly because men do not have the rapid bone loss attributed to the drop in estrogen levels at menopause, as is seen in women. Second, mortality and morbidity associated with hip fractures is higher in men than in women. Thirty to fifty percent of men with hip fractures die within one year as opposed to twenty percent of women. In men there is an identifiable underlying cause 50-70% of the cases as opposed to the majority cases of women, which are idiopathic.
Given this remarkable difference, men warrant a different osteoporosis work up than do women. Risk factors more commonly attributed to osteoporosis in men include chronic glucocorticoid use, hypogonadism, lifestyle (including alcohol consumption and smoking), hyperthyroidism, and vitamin D deficiency.
Glucocorticoids, often used in men treated for COPD, asthma, autoimmune disease and rheumatoid arthritis, suppress osteoblast activity and decrease small intestine absorption of calcium, leading to a loss of trabecular bone. This, in turn, stimulates PTH which increases osteoclastic resorption of bone. Hypogonadism is often seen in men with a history of prostate cancer treated with androgen blockade. This causes an increase in bone turnover with a significant loss of cancellous bone. Bisphophonates have been found to counteract the adverse effects of androgen blockade on bones. A randomized, double-blind, placebo-controlled study in 2000 from the NEJM of 241 men (age 31-97 with osteoporosis) found significant increases in percent change of lumbar spine, hip and total bone density in those treated with 70 mg of alendronate weekly. The study also found that alendronate treatment helped to prevent fractures and loss in height. In 2007, the Annals of Internal Medicine reported a randomized double-blind, placebo-controlled study of 112 men treated for non-metastatic prostate cancer with androgen deprivation therapy showing a statistically significant increase in bone density of the spine and femoral neck after 70 mg of weekly alendronate, calcium and vitamin D supplementation.
Lifestyle (alcohol, cigarettes, low calcium intake, inactivity) also plays a significant role in the development of osteoporosis, especially in men. Alcohol suppresses osteoblastic differentiation of bone marrow. It also decreases the synthesis of bone matrix after a fracture occurs. Alcohol consumption increases the risk of fall and therefore fractures. The mechanism of toxicity of tobacco on bones is unknown.
Despite these known risk factors and increased incidence found in men, there are no accepted screening guidelines. The International Society of Clinical Densometry and the Canadian Osteoporosis Society recommend DEXA scans for all men over the age of 70 and 65, respectively. However, the USPTF still has no official recommendations. Some red flags which should trigger a DEXA scan for male patients include known high-risk conditions (hypogonadism, prostate cancer treated with androgen antagonism, hyperthyroid, vitamin D deficiency), low-trauma fractures, incidental radiographic findings of osteopenia, and a loss of 1.5 inches in height. Osteoporosis in men has been defined as a T score >2.5 SDs below the mean observed in young adult women. Recently in JAMA, a study evaluating the cost per quality of life-year(QALY) gained support for checking bone density followed by five years of oral bisphosphonate therapy for men over age 65 without prior fracture, and for men over age 80 with prior fracture. New guidelines may soon appear.
If the DEXA scan is abnormal, the following tests should be checked:
• Serum testosterone, thyrotropin, calcium, alkaline phosphatase, 25-hydroxyvitamin 3, PTH
• Urinary calcium, creatinine
• BMP, hepatic panel to rule out renal and/or hepatic disease
• CBC and SPEP/UPEP to rule out hematological or myeloproliferative diseases
• Bone formation/resorption markers (these should not be obtained routinely)
• Iliac crest bone biopsy (after double tetracycline labeling) to differentiate osteoporosis from osteopenia
The treatment of osteoporosis men after treating identifiable causes and eliminating offending agents (glucocorticoids, alcohol, tobacco, meds) is similar to that in women. It includes calcium (1000-1200 mg/day) and vitamin D (800 IU/day) supplementation, weight bearing and muscle-strengthening exercise and fall prevention (vision correction, hearing evaluation, medication side effects, hip protectors). Pharmacologic treatment is also similar: bisphosphonates (alendronate/Fosamax, risendronate/Actonel inhibit osteoclast-mediated bone resorption), SERM (Raloxifene), and teriparatide/Forteo (PTH 1-34). The combination of bisphosphonates and teriparatide is not recommended. Calcitonin has been promising in studies in women, but has not yet been studied in men. Estradiol also holds promise but there is no true clinical evidence at this time. Growth hormone and Insulin-like growth factor-1 are also being evaluated for treatment of osteoporosis. Treatment monitoring is similar to that in women. A DEXA scan should be done every 1-2 years during treatment. Biochemical markers of bone turnover can also be used to monitor treatment response.
Osteoporosis in men is more common than most think. It plays a significant role in morbidity and mortality of our aging male population. More often than not, there is a treatable underlying cause in men and it is important to tune into pertinent medical histories and reviews of systems in attempt to diagnose and treat early.
Returning to our initial case, given the incidental finding on xray, GS was sent for a DEXA scan which revealed a T score of the vertebrae of -3.1. He was found to have a testosterone level of 120 (nl 400-800) and was started on hormone replacement, calcium and vitamin D supplementation.
References:
1)Campion, J.M. et al. “Osteoporosis in Men” Am Fam Physician 2003;67:1521-6.
2)Cauley, Jane A. “Osteoporosis in Men: Prevalence and Investigation” Clinical Cornerstone 1006;8(Suppl 3): S20-S25.
3)Greenspan, S.L. et al. “Effect of Once-Weekly Oral Alendronate on Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer.” The Annals of Internal Medicine. 2007;146:416-424.
4)Licata,A. “Osteoporosis in Men: Suspect secondary disease first” Cleveland Clinic Journal of Medicine 2003;70(3): 247-254.
5)Orwall, E. et al. “Alendronate for the Treatment of Osteoporosis in Men” NEJM, 2000; 343: 604-610.
6)Schousboe, J. et al. “Cost-effectiveness of Bone Densitometry Followed by Treatment of Osteoporosis in Older Men”. JAMA;298(6):629-637.
Uptodate.com “osteoporosis in men”