Statins, bone biology and revision arthroplasty: review of clinical and experimental evidence

Abstract

Osteoarthritis is a painful, disabling condition which is increasing in prevalence as a result of an ageing population. With no recognized disease-limiting therapeutics, arthroplasty of the hip and knee is the most common and effective treatment for lower limb osteoarthritis, however lower limb arthroplasty has a finite life-span and a proportion of patients will require revision arthroplasty. With increasing life expectancy and an increasing proportion of younger (<65 years) patients undergoing arthroplasty, the demand for revision arthroplasty after implant failure is also set to increase. Statins are cholesterol-modulating drugs widely used for cardiovascular risk reduction which have been noted to have pleiotropic effects including potentially influencing arthroplasty survival. In vitro studies have demonstrated pleiotropic effects in human bone cells, including enhancement of osteoblastogenesis following simvastatin exposure, and in vivo studies have demonstrated that intraperitoneal simvastatin can increase peri-implant bone growth in rats following titanium tibial implant insertion. There is evidence that statins may also influence osseointegration, enhancing bone growth at the bone–implant interface, subsequently improving the functional survival of implants. Data from the Danish Hip Arthroplasty Registry and the Clinical Practice Research Datalink in the UK suggest a reduction in the risk of lower limb revision arthroplasty in statin ever-users versus never-users, and a time-dependent effect of statins in reducing the risk of revision. In this article we review the clinical and experimental evidence linking statins and risk of revision arthroplasty.

How to Prevent Aseptic Loosening in Cementless Arthroplasty: A Review

“…As shown by the Danish Hip Arthroplasty Registry, statins reduce the risk of revision arthroplasty [72]. The mechanism can be explained by reduced cytokine production by the administration of statins.…”

Hedgehog signalling in bone and osteoarthritis: the role of Smoothened and cholesterol

“…Baudart et al (2017) [94] were unable to definitively report on the effects of statin use because there was insufficient information in the studies used for the meta-analysis. Sorial et al ( 2020) [87] reviewed the effects of statin use on OA and RA risk of arthroplasty treatment and reported a reduced risk of arthroplasty treatment in RA patients using statins, but not for OA patients. However, the complexity of the disease and confounding factors in the patient populations make it difficult to draw conclusions.…”

“…Aberrant HH signalling is implicated in several bone diseases such as RA, cartilaginous tumours, osteoporosis and OA [14][15][16][17][18][19][85][86][87][88]. In this review, we will focus on the role of HH signalling in OA as it is the most common joint disorder, and management of OA has significant worldwide socioeconomic impact.…”

“…Sorial et al. (2020) [87] reviewed the effects of statin use on OA and RA risk of arthroplasty treatment and reported a reduced risk of arthroplasty treatment in RA patients using statins, but not for OA patients. However, the complexity of the disease and confounding factors in the patient populations make it difficult to draw conclusions.…”

Bisphosphonates’ use and risk of aseptic loosening following total hip arthroplasty: a systematic review

“…The risk of AL based on the type of THA bearing surface, design, implant type, coating and porosity has been extensively studied so far (8,9,10,11). Several diseases, such as diabetes mellitus, rheumatoid arthritis, Parkinson's disease, previous surgical procedures, perioperative drug use, and other comorbidities, have also been evaluated (11,12,13,14,15,16,17). On top of that, there is growing interest in the peri-and post-operative use of anti-resorptive therapies, such as bisphosphonates (BPs), to mitigate the risk of THA AL.…”