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A 73-year-old man presents for follow-up after having sustained a wrist fracture aboard a cruise ship.
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A 73-year-old man presents for follow-up after having sustained a wrist fracture aboard a cruise ship. He had stumbled on the stairs but caught himself in time to prevent an outright fall. However, because wrist swelling and pain persisted, a radiograph was obtained, which revealed a typical Colles fracture of the left wrist. Further evaluation, including examination of the spine, revealed no other fracture.
The patient has mild essential hypertension, which is well controlled with an angiotensin-converting enzyme inhibitor. He also takes an ageappropriate multivitamin supplement. He has no history of prior fractures, corticosteroid therapy, diabetes mellitus, rheumatoid arthritis, or endocrine disorders. He is unaware of any family history of osteoporosis or hip fracture. He is retired, and his lifestyle is reasonably active. He goes to the gym 3 times a week and plays 1 round of golf per week. He does not smoke, and he has a single glass of red wine daily.
The patient appears his stated age. Body mass index is 26. Results of examination of the head, eyes, ears, nose, throat, lymph nodes, chest, and heart are all normal. Abdomen is nontender, and there are no masses or hepatosplenomegaly. Genitalia are normal, with no signs of hypogonadism. He has a cast on his left arm. A skeletal examination, including careful palpation along the vertebral column, reveals no other pain or bony deformity.
Hemogram is normal, as is the fasting blood glucose level. The serum creatinine level is 0.8 mg/dL; serum iron level, 110 μg/dL; transferrin level, 300 mg/dL (saturation, 33%); and ferritin level, 100 ng/mL. Results of liver function tests are normal. Serum testosterone level is 350 ng/dL.
Bone mineral density testing reveals a T score of −2.7 SD.
Which of the following represents optimal management for this patient?A. Monthly administration of intravenous pamidronate, 90 mg, or zoledronic acid, 4 or 5 mg at 6- to 12-month intervals, followed up with another bone density study in 3 years.
B. Monthly intramuscular testosterone injections.
C. A regimen of calcium supplements and weight-bearing exercise.
D. Oral bisphosphonate therapy, followed up with bone mineral density testing in 2 years.
CORRECT ANSWER: D
This patient sustained a fracture after what seemed like minor trauma; thus, he was appropriately evaluated for osteoporosis. Although no other fractures in more typical sites (eg, vertebrae) were found, results of bone mineral density testing were diagnostic of osteoporosis.
Osteoporosis in men. Osteoporosis is far more common in men than is generally appreciated. Its more usual presentations are hip fracture and loss of height. Secondary causes of osteoporosis are much more common in men than in women; they are found in roughly 60% of cases.1 The most frequently identified underlying cause is hypogonadism; other common causes include corticosteroid use and excessive alcohol intake.1 However, in 40% of cases, osteoporosis in men is classified as primary or idiopathic.
In this patient, an evaluation for secondary causes excluded the “major suspects” of corticosteroid use, low testosterone level, excessive alcohol use, and smoking. One additional study that was not ordered here but that generally should be included is measurement of the vitamin D level. Because of this patient's history of outdoor activity and use of a daily multivitamin, this study was not performed. In any event, supplementation will be prescribed for him as part of general therapy.
Osteoporosis in men is usually diagnosed in patients who are older than 70 years; increases in incidence accelerate after age 80. This patient's age is thus fairly typical.
Diagnosis of osteoporosis. Although there is some confusion and even controversy regarding the optimal diagnostic test, traditional bone densitometry is currently accepted as the preferred diagnostic technique (the femoral neck is the preferred location). Bone densitometry is used in both men and women.
Osteoporosis treatment. This patient has 2 major criteria for starting specific antiosteoporosis therapy: the presence of fracture with minimal trauma and a bone density T score of less than −2.5 SD.1,2 A vertebral fracture, even with less marked bone loss than is seen here, would be a third criterion.
Calcium supplements and weight-bearing exercise (choice C) are part of general osteoporosis prevention. Other general preventive measures include adequate vitamin D intake, smoking cessation, and avoidance of excess alcohol intake.1 These lifestyle measures are also appropriate as treatment in patients with less severe osteoporosis. However, in this patient, who has already experienced a fracture after minimal trauma, they would not be adequate therapy.
Testosterone therapy (choice B) has been used in male patients who have osteoporosis. However, data on its effectiveness are limited to its ability to increase bone mass; few, if any, studies have used the more clinically relevant end point of fracture. Moreover, the greatest effect of testosterone therapy has been seen in patients in whom hypogonadism was either clinically or biochemically present (with the latter defined as a serum testosterone level of less than 200 ng/dL). This man's testosterone level was well within the normal range. This fact, together with the potential adverse effects of testosterone (eg, polycythemia, prostate disease), makes choice B inappropriate here.3
This leaves bisphosphonates, the efficacy of which is supported by study data demonstrating improved bone densitometry scores, reduced fracture incidence, and even reduced mortality.1,2 The issue is which regimen would be best in this setting.
Intravenous bisphosphonate therapy (choice A), most authorities would agree, is probably too aggressive here. Excellent studies have demonstrated that a monthly regimen of intravenous pamidronate, 90 mg, and later zoledronic acid, 4 mg at 6- to 12-month intervals, reduces bony morbidity (eg, pathological fracture) in patients with multiple myeloma or breast cancer.2,4 There is also intriguing evidence that in addition to their effect on bone disease, pamidronate and zoledronic acid may have antineoplastic effects.4,5
However, in addition to the renal toxicity characteristic of all bisphosphonates, mandibular osteonecrosis has been observed with these agents.4,5 The risk of this condition is related to the type and duration of bisphosphonate exposure; a higher risk is seen with intravenous agents (in 1% to 14% of patients) compared with oral agents (in less than 0.3%), with zoledronic acid compared with pamidronate, and with longer durations of exposure.5 An oral agent (choice D) would thus be preferable here.
Follow-up. A program of general preventive and lifestyle measures was initiated, including calcium intake of at least 1200 mg per day and vitamin D intake of more than 800 IU per day. An oral bisphosphonate was prescribed. At 1 year, the patient has had no further fractures and his height is stable. A bone density study is planned at the 2-year interval.
REFERENCES:1. Ebeling PR. Clinical practice. Osteoporosis in men. N Engl J Med. 2008;358:1474-1482.
2. Lyles KW, ColÃ³n-Emeric CS, Magaziner JS, et al; HORIZON Recurrent Fracture Trial. Zoledronic acidand clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799-1809.
3. Amory JK, Watts NB, Easley KA, et al. Exogenous testosterone or testosterone with finasteride increasesbone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab. 2004;89:503-510.
4. Dodson TB, Raje NS, Caruso PA, Rosenberg AE. Case records of the Massachusetts General Hospital.
Case 9-2008. A 65-year-old woman with a nonhealing ulcer of the jaw. N Engl J Med. 2008;358:1283-1291.5. Durie BG, Katz M, Crowley J. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med. 2005;353:99