Effect of Teriparatide on Bone Formation in the Human Femoral Neck.

Abstract

Teriparatide (TPTD) improves bone mass and microstructure resulting in reduced risk of vertebral and nonvertebral fractures. However, hip bone mineral density improvements are modest and there are no data confirming that TPTD reduces hip fracture risk. To study the effects of TPTD on the proximal femur, we performed a double-blind trial of TPTD vs placebo (PBO) in patients with osteoarthritis from whom femoral neck (FN) samples were obtained at total hip replacement (THR) surgery. Participants were randomly assigned to receive TPTD or PBO for an average of 40 days before THR. Double tetracycline labeling was initiated 21 days prior to THR to allow histomorphometric assessment of bone formation. During the THR, an intact sample of the FN was procured, fixed, and sectioned transversely. Serum levels of bone turnover markers were measured at baseline and during the THR. Standard histomorphometric parameters were measured and calculated on four bone envelopes (cancellous, endocortical, intracortical, and periosteal). The primary outcome measure was bone formation rate/bone surface (BFR/BS). Forty individuals were enrolled (25 women, mean age, 71.5 ± 8.0 y and 15 men, mean age, 68.9 ± 7.7 y). In cancellous and endocortical envelopes, BFR/BS was 100% higher in the TPTD vs PBO group (P < .05). Bone turnover markers measured at the time of THR correlated with BFR/BS. TPTD stimulates bone formation rapidly in cancellous and endocortical envelopes of the FN. Our findings provide a mechanistic basis for TPTD-mediated improvement in FN bone mass and ultimately hip strength. This study is the first demonstration of the effect of any osteoporosis medication on osteoblast activity in the human proximal femur.