Parathyroid hormone as a therapy for idiopathic osteoporosis in men: Effects on bone mineral density and bone markers

Osteoporosis in men poses a unique therapeutic challenge. Clinical studies have focused largely on the more prevalent problem of postmenopausal osteop orosis, with few gender-specific studies exploring treatment options in men . Idiopathic osteoporosis in middle-aged men presents an additional dilemma , because in the majority of patients it is a low bone turnover state for w hich there are currently no available anabolic agents. We conducted an 18-month randomized, double blind, placebo-controlled trial of 23 men with idiopathic osteoporosis, 30-68 yr old (mean age +/- SEM, 50 +/- 1.9 yr). All patients received 1500 mg calcium and 400 IU vitamin D da ily. Ten patients were randomized to receive 400 IU PTH-(1-34), and 13 pati ents received vehicle, administered by daily sc injection. Serum and urinar y biochemistries, including markers of bone turnover were measured every 3 months. Bone densitometry of the lumbar spine, hip, and radius was performe d every 6 months. PTH-(1-34) was associated with a marked 13.5% increase in bone mass at the lumbar spine, whereas that in the control group did not change (P < 0.001). The mean lumbar spine T-score improved from -3.5 +/- 0.2 to -2.4 +/- 0.4. Femoral neck bone mineral density in the PTH-treated group increased 2.9% ( P < 0.05). The 1/3 site of the distal radius showed no change from baseline in the PTH-treated group. There were no significant changes in serum calci um concentration, 24-h urinary calcium excretion, or 1,25-dihydroxyvitamin D in either group. All markers of bone turnover increased in the PTH-treate d patients, with the greatest changes in serum osteocalcin and urinary N-te lopeptide (23% and 375% above baseline by 12 months, respectively; P < 0.00 1). Free pyridinoline and markers of bone formation that showed little corr elation with each other at baseline, became highly correlated in the PTH-tr eated group (r = 0.1; P = 0.29 at baseline; to r = 0.7; P < 0.0001 at 18 mo nths), a pattern absent in the control patients. The best predictor of the lumbar spine response to PTH at 18 months was the combination of pyridinoli ne at baseline and osteocalcin at 3 months (70% of the variance). PTH is a potent stimulator of skeletal dynamics in men with idiopathic, low turnover osteoporosis; is associated with substantial increases in lumbar spine and hip bone density; and may prove to be an efficacious anabolic age nt in men with this disorder.