Bone Histomorphometry in Hypogonadal and Eugonadal Men with Spinal Osteoporosis*

We present iliac bone histomorphometric data after in vivo double tetracycline labeling and related biochemical data from 14 nonalcoholic men referred for evaluation of symptomatic spinal osteoporosis. Six patients had previously undiagnosed hypogonadism, and 8 had normal gonadal function and no evident etiology for osteoporosis. Bone histomorphometry revealed no differences in structural measurements or resorption indices between the 2 groups. However, compared to reference values for normal postmenopausal women, osteoblast surface, mineralizing surface, and formation rate were normal or modestly increased in the hypogonadal men and significantly reduced in the idiopathic group. There were significant corresponding differences between the 2 groups in the fasting urinary hydroxyproline to creatinine ratio, an index of bone resorption, and serum total alkaline phosphatase, an index of bone formation. Plasma 25-hydroxyvitamin D levels did not differ between the 2 groups and were above 10 ng/mL in all patients. Plasma 1,25-dihydroxyvitamin D 1,25-(OH)2D levels were normal in the hypogonadal group and significantly reduced in the idiopathic group, but did not correlate with any histological measurements. The formation indices fell substantially in 3 of 4 hypogonadal men after 7-14 months of therapy with testosterone and a calcium supplement. We conclude the following. In vitamin D-replete hypogonadal men with osteoporosis, 1,25-(OH)2D synthesis is normal, and bone remodeling is modestly increased and correctable by hormone replacement therapy, as in normal postmenopausal women. In middle-aged men with idiopathic osteoporosis, there is impairment of 1,25-(OH)2D synthesis and of the recruitment and activity of teams of osteoblasts, as in postmenopausal osteoporosis.