This thesis starts with a comprehensive review of the literature on the role of vitamin D in fracture healing. Followed by three clinical studies on the prevalence of vitamin D deficiency in... Show moreThis thesis starts with a comprehensive review of the literature on the role of vitamin D in fracture healing. Followed by three clinical studies on the prevalence of vitamin D deficiency in fracture patients, risk factors and effect of vitamin D status on fracture healing. The second part of this thesis begins with an extensive review on the effect of osteoporosis and its treatment on fracture healing. A retrospective study is performed on the effect of osteoporosis on fracture healing. Also a more fundamental study on osteoporosis is performed, levels of sclerostin are determined in fracture patients with osteoporosis as biomarker. In the appendix of this thesis, two case reports are presented which illustrate the role of vitamin D plays in bone metabolism and fracture healing.Overall, vitamin D plays a role in fracture healing, although the exact mechanismremains not fully elucidated. The influence of vitamin D deficiency on fracturehealing cannot be fully ignored, but the exact degree of influence is not determined yet.Since the high prevalence of vitamin D deficiency found among adult and paediatricfracture patients, clinicians should be aware of vitamin D deficiency and the prevailingadvice regarding vitamin D supplementation, especially in case of delayed fractureunion or fracture non union.Although animal studies show a negative effect of osteoporosis on fracture healing,convincing clinical evidence lack to support this potential association. Since no negativeeffect of anti-osteoporosis medication on fracture healing could be determined inpatients, treatment should not be withheld in case of a fracture. Show less
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... Show morePurpose 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. Show less
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,... Show moreIntroduction: 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. Show less
Introduction: Animal models indicate that osteoporosis may negatively influence the fracture healing process, but clinical studies on this topic are scarce. In this study we investigated the effect... Show moreIntroduction: Animal models indicate that osteoporosis may negatively influence the fracture healing process, but clinical studies on this topic are scarce. In this study we investigated the effect of osteoporosis on fracture healing in patients with an upper extremity fracture.Methods: This retrospective cohort study included all patients aged 50 years or older, with a fracture of the proximal humerus or the distal radius treated in the period June 2012 to July 2015 and a DEXA scan within a year after fracture. The incidence of delayed-union and non-union were compared between patients with or without osteoporosis (BMD T score <= -2.5SD). A secondary analysis was performed with a more pragmatically definition; BMD T score <= -2.5SD or a proximal humerus fracture with a T-score between -2.5SD and -1.0SD.Results: Osteoporosis was diagnosed in 133/455 patients (29.2%). A total of 461 fractures (distal radius n = 311 and proximal humerus n = 150) were treated. Radiological delayedor non-union was described in 11/461 cases (2.4%); all proximal humerus fractures of which 6 cases (1.3%) were clinically manifest. The incidence of delayedor non-union in fracture treatment did not differ between patients with osteoporosis (5/137 fractures) and the patients without osteoporosis (6/324 fractures) (p = 0.27). In the second analysis a significantly higher incidence was found in patients with osteoporosis (10/214 fractures vs 1/247 fractures p = 0.003)Conclusions: The results of this study suggest that osteoporosis does not significantly influence the progress of fracture healing in distal radius and proximal humerus fractures, although there seems to be a tendency towards a negative effect. Show less
Amelung, F.J.; Borstlap, W.A.A.; Consten, E.C.J.; Veld, J.V.; Halsema, E.E. van; Bemelman, W.A.; ... ; Dutch Snapshot Res Grp 2019
Background: Although self-expandable metal stent (SEMS) placement as bridge to surgery (BTS) in patients with left-sided obstructing colonic cancer has shown promising short-term results, it is... Show moreBackground: Although self-expandable metal stent (SEMS) placement as bridge to surgery (BTS) in patients with left-sided obstructing colonic cancer has shown promising short-term results, it is used infrequently owing to uncertainty about its oncological safety. This population study compared long-term oncological outcomes between emergency resection and SEMS placement as BTS.Methods: Through a national collaborative research project, long-term outcome data were collected for all patients who underwent resection for left-sided obstructing colonic cancer between 2009 and 2016 in 75 Dutch hospitals. Patients were identified from the Dutch Colorectal Audit database. SEMS as BTS was compared with emergency resection in the curative setting after 1: 2 propensity score matching.Results: Some 222 patients who had a stent placed were matched to 444 who underwent emergency resection. The overall SEMS-related perforation rate was 7.7 per cent (17 of 222). Three-year locoregional recurrence rates after SEMS insertion and emergency resection were 11-4 and 13.6 per cent (P= 0-457), disease-free survival rates were 58-8 and 52.6 per cent (P= 0-175), and overall survival rates were 74-0 and 68-3 per cent (P= 0.231), respectively. SEMS placement resulted in significantly fewer permanent stomas (23.9 versus 45.3 per cent; P < 0-001), especially in elderly patients (29.0 versus 57.9 per cent; P < 0-001). For patients in the SEMS group with or without perforation, 3-year locoregional recurrence rates were 18 and 11.0 per cent (P= 0.432), disease-free survival rates were 49 and 59.6 per cent (P= 0-717), and overall survival rates 61 and 75.1 per cent (P= 0.529), respectively.Conclusion: Overall, SEMS as BTS seems an oncologically safe alternative to emergency resection with fewer permanent stomas. Nevertheless, the risk of SEMS-related perforation, as well as permanent stoma, might influence shared decision-making for individual patients. Show less
