Are There Biological Markers for Wear or Corrosion? A Systematic Review

Abstract

Background Identification of biomarkers associated with wear and tribocorrosion in joint arthroplasty would be helpful to enhance early detection of aseptic loosening and/ or osteolysis and to improve understanding of disease progression. There have been several new reports since the last systematic review (which covered research through mid-2008) justifying a new assessment. Questions/purposes We sought to determine which biomarkers have the most promise for early diagnosis and monitoring of aseptic loosening and/or osteolysis related to wear or corrosion in total joint arthroplasty. Methods We performed a systematic review using MED-LINE and EMBASE databases, covering the period through December 2013, and identified 1050 articles. We restricted the definition of biomarker to biomolecules and imaging parameters useful for diagnosis and monitoring of disease progression, only including articles in English. We chose 65 articles for full review, including 44 from the original search and 21 from subsequent hand searches. We used the 22 articles in which patients with total joint arthroplasty who had aseptic loosening and/or periimplant osteolysis unrelated to sepsis had been compared with patients with total joint arthroplasty with stable implants. There were 90 comparisons of these two patient populations involving 35 different biomarkers. Results Diagnostic accuracy was assessed in nine of the 90 comparisons with the highest accuracy found for tartrateresistant acid phosphatase 5b (0.96), although a separate comparison for this biomarker found a lower accuracy (0.76). Accuracy of [ 0.80 was also found for crosslinked n-telopeptide of type I collagen, osteoprotegerin, and deoxypyridinoline. The most studied markers, tumor necrosis factor-a and interleukin-1b, were found to differ in the affected and control groups in\30% of the comparisons. Thirty of the 35 biomarkers were studied in four or fewer separate comparisons with nearly half of the biomarkers (17) studied in only one comparison. Many of the comparisons were not able to eliminate a number of confounding variables, and there was only one prospective study. Conclusions Currently, there are no validated biomarkers for early diagnosis and monitoring of the biological sequelae of wear or tribocorrosion, although there are some promising leads, including markers of bone turnover.

Adverse local tissue reaction (ALTR) associated with corrosion products in metal‐on‐metal and dual modular neck total hip replacements is associated with upregulation of interferon gamma‐mediated chemokine signaling

“…Despite the continued significant clinical problems associated with implant failure due to peri‐implant osteolysis and/or ALVAL reactions, there remains a lack of approved medical therapies or circulating biomarkers for treatment and monitoring of patients at‐risk of implant failure. A recent systematic review highlighted the paucity of validated data on biomarkers for osteolysis or tribocorrosion‐associated ALTR . The most promising putative biomarkers for peri‐implant osteolysis are restricted to markers of increased bone turnover, and consistent with this such biomarkers are elevated systemically in animal models of localized wear‐induced osteolysis and osteoclast products are elevated in peri‐implant tissues of osteolysis patients .…”

Discovery of biomarkers to identify peri‐implant osteolysis before radiographic diagnosis

“…Thus, our focus was on discovery. Future validation work in independent cohorts is needed 17 . Additionally, the study suffered from missing values at various points during the longitudinal follow-up period, which prevented repeated measures statistics.…”

“…The use of noninvasive or minimally invasive biomarkers to monitor patients post-surgery would provide real-time information on peri-implant inflammation or bone resorption, which in turn could be used to identify patients at risk for osteolysis. To date, biomarker studies in patients have been inconsistent and at times contradictory 17 . The major limitation of current biomarker research is that most studies only assess marker levels at the end-stage of osteolysis.…”

Laboratory techniques for diagnosing and risk evaluation for complications after arthroplasty of large joints. An analytical review

“…имеется ряд недостатков в части их научной доказа-тельности: исследования количественных характери-стик (чувствительность, специфичность) тестов про-ведены по данным ретроспективных исследований, в работах отсутствовали в полной степени сопостави-мые группы сравнения, отсутствует стандартизация методик анализа и единства протокола их выполнения (порядок и сроки контрольного осмотра после ЭКС). Тем не менее, перспективность дальнейшего клини-ческого использования указанных маркеров костного обмена очевидна [12]. Тем более, что для диагностики и прогноза асептической нестабильности после ЭКС в настоящее время предлагается использовать указанные в таблице 1 маркеры в едином комплексе, техническая возможность (использование чипов) такого подхода вполне реализуема [20].…”

“…Также пока существует мало доказательств инфор-мативности иммунологических тестов для целей ранней диагностики и оценки рисков развития асептической нестабильности [12]. Хотя имеются работы, в которых показана высокая корреляция между ростом уровня не-которых иммунологических показателей (IL-6, TNFα, CD14+HLA-DR) и развитием асептической нестабиль-ности [27].…”