The effect of osteoporosis and its treatment on fracture healing a systematic review of animal and clinical studies

Introduction: Osteoporosis is characterised by low bone mass and micro-architectural deterioration of bone structure. Its treatment is directed at the processes of bone formation or resorption, that are of utmost importance in fracture healing. We provide a comprehensive review of the literature aiming to summarize and clarify the effects of osteoporosis and its treatment on fracture healing. Material and methods: A literature search was conducted in PubMed and Embase (OVID version). In vivo animal and human studies on long bone fractures were included. A total of 93 articles were included for this review; 23 studies on the effect of osteoporosis (18 animal and 5 clinical studies) and 70 studies on the effect of osteoporosis treatment (41 animal, 26 clinical studies and 3 meta-analyses) on fracture healing. Results: In animal fracture models osteoporosis was associated with decreased callus formation and bone growth, bone mineral density, biomechanical strength and delayed cellular and differentiation processes during fracture healing. Two large databases identified osteoporosis as a risk factor for non-union whereas three other studies did not. One of those three studies however found a prolonged healing time in patients with osteoporosis. Antiosteoporosis medication showed inconsistent effects on fracture healing in both non-osteoporotic and osteoporotic animal models. Only the parathyroid hormone and anti-resorption medication were related to improved fracture healing and delayed remodelling respectively. Clinical studies performed in predominantly hip and distal radius fracture patients showed no effect of bisphosphonates on fracture healing. Parathyroid hormone reduced time to union in several clinical trials performed in mainly hip fracture patients, but this did not result in decreased delayed or non-union rates. Conclusion: Evidence that substantiates the negative influence of osteoporosis on fracture healing is predominantly from animal studies and to a lesser extent from clinical studies, since convincing clinical evidence lacks. Bisphosphonates and parathyroid hormone may be used during fracture healing, since no clear negative effect has been shown. Parathyroid hormone might even decrease time to fracture union, without decreasing union rate.