Treatment of postmenopausal osteoporotic women with parathyroid hormone 1-84 for 18 months increases cancellous bone formation and improves cancellous architecture: a study of iliac crest biopsies using histomorphometry and micro computed tomography.

Histomorphometry studies in rhesus monkeys have shown that daily treatment with full-length parathyroid hormone 184 (PTH) increases bone formation and bone volume. However, there is no published information on the effects of PTH treatment on bone microarchitecture in humans. We obtained iliac crest biopsies from postmenopausal osteoporotic women given daily injections of placebo or 100 Ìg PTH for 18 months to assess the effects of treatment on cancellous and cortical bone formation and structure. All subjects received background treatment with Ca (700 mg) and vitamin D (400 IU). At baseline there were no significant differences between groups in age, weight, bone turnover markers, and spine and hip bone mineral density. Intact biopsies were collected from 8 placeboand 8 PTHtreated women at month 18. Prior to sectioning for histomorphometry, the biopsies were subjected to micro-computed tomography (ÌCT) to quantify the 3-D and 2-D structure of trabecular and cortical bone, respectively. The results of the histomorphometric and ÌCT analyses are summarized in Table 1. Cancellous bone formation rate (BFR) was significantly higher in PTH-treated subjects and was primarily the result of an increased mineralizing surface (MS/BS); mineral appositional rate (MAR) was not increased significantly. Osteoblast and osteoid surfaces were 58% and 35%, respectively, higher in the PTH-treated group, but the increases were not significant. No index of bone resorption was significantly affected by PTH treatment, although a trend towards increased activation frequency (Ac.F) was noted. Maintenance of elevated BFR at month 18 was confirmed by measurement of serum levels of the bone formation marker, bone-specific alkaline phosphatase, which were 38% higher in PTH-treated subjects than in the placebo group at month 18. Values for cancellous bone structure and the differences between groups were very similar whether obtained by histomorphometry or by ÌCT. Trabecular bone volume (BV/TV) measured by histomorphometry was 48% higher in subjects treated with PTH; this increase was the combined effect of 24 and 17% higher trabecular number (Tb.N) and thickness (Tb.Th), respectively, and resulted in a 21% lower trabecular separation (Tb.Sp). The increase in Tb.N appeared to result from the splitting of thickened trabeculae by tunneling osteoclasts. Trabecular connectivity (Conn.D) measured by ÌCT was 22% higher and the structure model index (SMI) was 55% lower in PTH-treated subjects. A reduction in SMI indicates a change in trabecular architecture from a rod-like to a more plate-like structure. No significant effects of PTH treatment were observed on periosteal or endocortical BFR, or on cortical thickness (Ct.Th) or porosity (Ct.Po). There was a >60% mean difference in Ct.Th between the 2 cortices of the iliac crest; the J Musculoskelet Neuronal Interact 2005; 5(4):356-357