Based on its proven
anabolic effects on bone in
osteoporosis patients, recombinant
parathyroid hormone (PTH(1-34)) has been evaluated as a potential
therapy for skeletal repair. In animals, the effect of
PTH(1-34) has been investigated in various skeletal repair models such as fractures,
allografting, spinal
arthrodesis and
distraction osteogenesis. These studies have demonstrated that intermittent
PTH(1-34) treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore,
PTH(1-34) has been shown to enhance bone repair in challenged animal models of aging, inflammatory
arthritis and
glucocorticoid-induced bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting
PTH(1-34) treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of
PTH(1-34) treatment of patients with
radius fracture has failed to achieve its primary outcome, largely because of effective healing in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the appropriate patient population for
PTH(1-34) therapy in skeletal repair. Here, we review our current knowledge of the effects of
PTH(1-34) therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications) and discuss the long-term potential of this
drug as an adjuvant for endogenous tissue engineering.