Teriparatide Following Bisphosphonates: Initial and Long-Term Effects on Microarchitecture and Bone Remodeling at the Human Iliac Crest

Abstract

Since the approval of teriparatide for clinical application, a number of iliac crest studies have focused on increases in bone volume or changes in structural parameters with microCT and numerical changes in histomorphometry. This investigation is based on individual histopathological observations related to early and late effects of teriparatide treatment in humans. A total of 44 (18 paired) iliac crest biopsies (ICB) from 41 patients receiving teriparatide (10 months ± 6 months) following bisphosphonate (BP) treatment were investigated for hematopoietic changes, bone turnover, and description of microarchitectural changes using histology and selective microCT. Fully 71% of the ICB showed a normal or high bone turnover; 56% of the paired ICB presented an increase in bone turnover following teriparatide treatment. Early teriparatide stimulation (<1 month) resulted in peritrabecular fibroblast-like formations. Rare findings (<9%) included reactive hematopoietic changes, osteoidosis, endosteal fibrosis, microcallus, or woven bone. Round mast cells were frequently observed within marrow spaces. A total of 14% had an increase in cortical porosity, ∼20% demonstrated signs of intratrabecular resorption sites. Teriparatide treatment resulted in an increase in remodeling units as early as 1 week after the first application with a continuous stimulation up to 18 months of rhPTH treatment despite previous BPs. Subgroups of patients developed increased cortical and/or intratrabecular resorption pattern, with unclear biomechanical significance. This mechanism could potentially result in new trabecular structures with an increase in trabecular number. Some individuals presented histological findings (e.g., fibrosis) that may require adjustment of treatment that could be of importance for clinical efficacy.