J. Mark Wilkinson

Bone mineral density and biochemical markers of bone turnover in aseptic loosening after total hip arthroplasty.

The aims of this study were to determine whether subjects with aseptic loosening after total hip arthroplasty (THA) have regional differences in periprosthetic bone mineral density (BMD) and systemic biochemical markers of bone turnover compared to subjects with successful implants.

Bisphosphonates in orthopedic applications

Bisphosphonates (BPs) exert potent effects on the skeleton. As such, there are important questions relating to how treatment with BPs for metabolic disorders might affect outcomes of orthopedic problems. A further question is what role, if any, might BPs play as adjunctive therapeutics for orthopedic problems. This article outlines the research thus far in the application of BPs to the management of osteonecrosis, bone repair, and joint arthroplasty. Many animal studies show a benefit to decreasing bone resorption in models of osteonecrosis. These include studies in both small and large animals, backed up by limited human data. Further clinical trials are underway for this indication. In bone repair, again, multiple studies exist. There are concerns that BPs could interfere with the normal processes of healing. Some of the controversy about benefits or adverse effects of BPs in this context can be distilled down to effects of dosing and administration. With some exceptions, longer intervals between dosing seem to be more beneficial while not producing adverse healing effects in animal studies. In joint arthroplasty, animal studies suggest a role for topical or systemic BPs for enhancing bone on-growth to implant surfaces and strength of mechanical fixation, although these are yet to be confirmed in clinical studies. Clinical studies show that BPs inhibit periprosthetic bone loss due to strain-adaptive remodeling and after impaction bone grafting, although an efficacy in inhibiting inflammatory bone loss due to wear particle-induced osteolysis has not been confirmed. Lastly, as anabolic drugs have become available, there is increasing interest in their combined use with BPs. From experimental data, manipulation of both the anabolic and catabolic responses is a powerful approach in models of bone repair.

Biochemical markers of bone turnover and development of heterotopic ossification after total hip arthroplasty

We studied biochemical markers of bone turnover markers in 20 men and women over 26 weeks after total hip arthroplasty (THA) in order to characterize the changes in bone metabolism associated with developing heterotopic ossification (HO). Transient increases in biochemical markers of both osteoclast and osteoblast activity occurred after surgery. Subjects developing HO (n = 9) had greater rises in the osteoclast marker C‐telopeptide of type‐I collagen (CTX‐I; ANOVA P = 0.004), and the osteoblast markers N‐terminal propeptide of type‐I procollagen (PINP; ANOVA P − 0.01) and osteocalcin (OC; ANOVA P − 0.02) than those who did not develop HO. A rise of > 42% in CTX‐I at one week after surgery had a sensitivity of 89% and a specificity of 82% for predicting HO development at week 26 (P < 0.05). Rises of > 57% in PINP and > 13% in OC at week 6 had sensitivities of 89% and 56%, and specificities of 82% and 91%, respectively for development of HO. Transient increases in osteoblast and osteoclast activity occur after THA. These changes are greater in patients developing HO than in those who do not develop HO. The potential applications of these markers are as a non‐invasive, radiation‐free tool for investigating the pathogenesis of HO, and as an early surrogate outcome marker for HO development in clinical trials of novel prophylaxis regimes for its prevention.

Statistical Shape and Appearance Models in Osteoporosis

Statistical models (SMs) of shape (SSM) and appearance (SAM) have been acquiring popularity in medical image analysis since they were introduced in the early 1990s. They have been primarily used for segmentation, but they are also a powerful tool for 3D reconstruction and classification. All these tasks may be required in the osteoporosis domain, where fracture detection and risk estimation are key to reducing the mortality and/or morbidity of this bone disease. In this article, we review the different applications of SSMs and SAMs in the context of osteoporosis, and it concludes with a discussion of their advantages and disadvantages for this application.

High-spatial-resolution bone densitometry with dual-energy X-ray absorptiometric region-free analysis.

PURPOSEnTo outline the conceptual development of dual-energy absorptiometric (DXA) region-free analysis, quantify its precision, and evaluate its application to quantify the change in longitudinal femoral periprosthetic bone mineral density (BMD) in patients during the 12 months after total hip arthroplasty.nnnMATERIALS AND METHODSnAll subjects had undergone total hip arthroplasty for idiopathic arthritis, and the scans were collected as part of previous ethically approved studies (1998-2005) for which informed consent was provided. Contemporary image processing approaches were used to develop a region of interest-free DXA analysis method with increased spatial resolution for assessment of proximal femoral BMD. The method was calibrated, and its accuracy relative to a proprietary algorithm was assessed by using a hip phantom. The precision of the method was examined by using repeat DXA acquisitions in 29 patients, and its ability to allow spatial resolution of localized periprosthetic BMD change at the hip was assessed in an independent group of 19 patients who were measured throughout a 12-month period. Differences were evaluated with t tests (P < .05).nnnRESULTSnThe method allowed spatial resolution of more than 10 000 individual BMD data points on a typical archived prosthetic hip scan. The median data point-level error of the method after calibration was -1.9% (interquartile range, -7.2% to 3.5%) relative to a proprietary algorithm. The median data point-level precision, expressed as a coefficient of variation, was 1.4% (interquartile range, 1.2%-1.6%). Evaluation of BMD change in a model of periprosthetic bone loss demonstrated large but highly focal changes in BMD that would not be resolved by using traditional region of interest-based analysis approaches.nnnCONCLUSIONnThe proposed approach provides a quantitative, precise method for extracting high-spatial-resolution BMD data from existing DXA datasets without the limitations imposed by region of interest-based analysis.

Risk Factors for Aseptic Loosening Following Total Hip Arthroplasty

Total hip arthroplasty (THA) is one of the most successful orthopaedic procedures and has relieved pain and improved hip function in millions of patients worldwide. Despite the success of modern prosthetic designs and bearing surfaces, around 10% of THA prostheses still fail within 10 years1. Improvements in surgical technique and prosthesis design have decreased the incidence of deep sepsis, dislocation and fracture, however aseptic loosening, the clinical end point of osteolysis, remains the most frequent complication and in the UK accounts for 63% of all revision surgery (Table 1)2. Prosthesis loosening results in pain and disability, requiring revision surgery. Revision THA is associated with a 3 to 8-fold greater in-hospital mortality, poorer functional outcome, longer hospital stay, and higher cost than primary surgery1,3-5. The problem of osteolysis has been recognized in Judet’s acrylic hemiarthroplasty introduced in the 1940s. Prosthesis loosening complicating THA in the 1950’s and 1960’s was poorly understood and attributed to unconfirmed sepsis6 and prosthesis motion7. In the 1980’s loosening was thought to be the result of “cement disease”8, arising due to a foreign body reaction to methyl methacrylate. When the development of cementless prostheses

Effect of Pamidronate on Excretion of Pyridinium Crosslinks of Collagen After Total Hip Arthroplasty

Periprosthetic bone loss is an important factor that limits implant survival after total hip arthroplasty (THA). In a randomized trial we previously reported that pamidronate therapy prevented periprosthetic bone loss and decreased urinary excretion of N-telopeptide collagen cross-links over the first 6 months after THA, but had no apparent effect on free deoxypyridinoline excretion (J Bone Miner Res 2001; 16:556–564). In this study we investigated this discrepant observation that pamidronate reduced conjugated cross-link excretion but had no effect on free cross-links. Free and total deoxypyridinoline (DPD) were assayed by reverse-phase high-performance liquid chromatography (HPLC) and by immunosorbent assay (ELISA) at preoperative baseline and at week 6 after surgery in 46 subjects who had taken part in the trial. Randomly selected, 22 subjects received a single 90 mg intravenous infusion of pamidronate and 24 received placebo. Acute rises in free and total DPD occurred in both study groups at week 6 (P < 0.05). Total DPD excretion was lower in the pamidronate group than in the placebo group when measured by both HPLC and ELISA (P < 0.05). No difference in free DPD was found between groups. A rise in the ratio of free to total DPD occurred in the pamidronate group at week 6 (P = 0.03), but not in the placebo group. Pamidronate treatment suppresses excretion of total DPD. This is consistent with the effect of pamidronate on other turnover markers and periprosthetic bone loss after THA. Urinary-free DPD is a poor marker of response to treatment as the ratio of free-to-total cross-links is affected by amino-bisphosphonate therapy.

Use of high resolution dual-energy x-ray absorptiometry-region free analysis (DXA-RFA) to detect local periprosthetic bone remodeling events

Dual‐energy x‐ray absorptiometry (DXA) is the gold standard method for measuring periprosthetic bone remodeling, but relies on a region of interest (ROI) analysis approach. While this addresses issues of anatomic variability, it is insensitive to bone remodeling events at the sub‐ROI level. We have validated a high‐spatial resolution tool, termed DXA‐region free analysis (DXA‐RFA) that uses advanced image processing approaches to allow quantitation of bone mineral density (BMD) at the individual pixel (data‐point) level. Here we compared the resolution of bone remodeling measurements made around a stemless femoral prosthesis in 18 subjects over 24 months using ROI‐based analysis versus that made using DXA‐RFA. Using the ROI approach the regional pattern of BMD change varied by region, with greatest loss in ROI5 (20%, pu2009<u20090.001), and largest gain in ROI4 (6%, pu2009<u20090.05). Analysis using DXA‐RFA showed a focal zone of increased BMD localized to the prosthesis–bone interface (30–40%, pu2009<u20090.001) that was not resolved using conventional DXA analysis. The 20% bone loss observed in ROI5 with conventional DXA was resolved to a focal area adjacent to the cut surface of the infero‐medial femoral neck (up to 40%, pu2009<u20090.0001). DXA‐RFA enables high resolution analysis of DXA datasets without the limitations incurred using ROI‐based approaches.