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. Anti-osteoporosis 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.

Purpose Sclerostin inhibits bone formation and stimulates bone resorption. Previous studies found a positive association between bone density and serum sclerostin, but literature on sclerostin levels in osteoporotic fracture patients is scarce. The aim of the present study was to compare the serum sclerostin levels in osteoporotic and non-osteoporotic fracture patients and to assess the correlation of the sclerostin levels with bone mineral density and vitamin D status. Methods In this cross-sectional study, we included patients over 50 years, with an extremity fracture after low-energy trauma treated between 2012 and 2018, with biobank samples and available bone density measurements by Dual X-ray Absorption. Osteoporosis was diagnosed according the World Health Organisation criteria. Vitamin D deficiency was defined as a 25(OH)D concentration < 30 nmol/L. After defrosting biobank samples, serum sclerostin was measured using the human SOST (sclerostin) enzyme-linked immunosorbent assay kit. We prespecified a subgroup analysis including only female patients. Results 179 patients were included of whom 139(78%) were female. In 46 patients (25.7%), osteoporosis was diagnosed. Bone mineral density was positively associated with sclerostin levels (r = 0.17, p = 0.026) and patients with osteoporosis had a significantly lower serum sclerostin compared to non-osteoporotic fracture patients (mean 41.9 pmol/L vs 48.1 pmol/L; p = 0.03). This difference remained significant after correction for potential confounders. Similar results were found in the subgroup of female patients. No association between serum sclerostin and vitamin D deficiency was found. Conclusion Osteoporotic fracture patients had lower levels of sclerostin than non-osteoporotic fracture patients. Future research should focus on the use of sclerostin as biomarker for osteoporosis in fracture patients.