Does early PTH treatment compromise bone strength? The balance between remodeling, porosity, bone mineral, and bone size.
The treatment of osteoporotic women with recombinant human parathyroid hormone (rhPTH) increases bone mineral density and reduces fracture risk. However, there has been concern that the initiation of therapy in women with low bone mass may cause an early and transient increased fracture risk because PTH stimulates bone remodeling, which in its first phase is associated with bone resorption. Animal and human studies suggest, however, that the stimulation of remodeling caused by rhPTH(1-34) does not lead to a deterioration of bone's mechanical properties or to an increased fracture risk even early in the treatment. There are several reasons for this. Bone biomarkers associated with formation rise earlier than those associated with resorption, suggesting that there is an initial period prior to the stimulation of remodeling during which bone formation occurs on surfaces without prior resorption. This initial period of formation may protect the patient from the later small and transient losses that occur through remodeling. Moreover, the increased remodeling occurs on cancellous surfaces or close to the endosteal surface of bone, where its mechanical effect is minimal. Additionally, these transient losses may be compensated by periosteal apposition that maintains the overall strength of the bone. Thus, the early stimulation of bone formation without prior resorption, and the redistribution of bone from cancellous and endocortical surfaces to the periosteal surface combine to prevent the mechanical deterioration that could otherwise occur with a transient acceleration of bone remodeling in a patient with low bone mass.
Burr
David B
DB
Department of Anatomy and Cell Biology, MS 5035, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA. dburr@iupui.edu
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D016062:Porosity; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012307:Risk Factors; D013268:Stimulation, Chemical; D019379:Teriparatide / Q000627:therapeutic use*; D013997:Time Factors
D015415:Biomarkers; D011994:Recombinant Proteins; D019379:Teriparatide