Thrombophilia-associated factors in patients with spontaneous osteonecrosis of the knee

Introduction: Spontaneous osteonecrosis of the knee (SONK) is the most common of three types of knee osteonecrosis. While thrombophilia has been shown to play a role in the pathogenesis of femoral head osteonecrosis and in multifocal osteonecrosis syndrome, this has never been tested as a possible factor in the pathogenesis of SONK. Therefore, this study was designed to test whether patients with SONK are characterized by abnormal levels of thrombophilia-associated factors.

Materials and methods: Twenty-five patients with SONK were recruited. Inclusion criteria were: (1) Age> 40 years; (2) acute onset knee pain not precipitated by trauma; and (3) MRI findings consistent with SONK. Exclusion criteria were: (1) history of cancer and chemotherapy, and (2) factors associated with secondary osteonecrosis. Blood tests included 13 thrombophilia-associated factors which were either heritable mutations or acquired factors. Descriptive statistics included medians, ranges, means, and standard deviations. Mann-Whitney test was used to compare thrombophilia-associated factor levels between the sexes. Spearman`s rank test was used to test correlations between smoking status and each thrombophilia-associated factor. Level of significance was set at 0.05.

Results: Patient age was median 62 years (range, 44-77). Thirteen (52%) patients had thrombophilia-associated factor abnormalities of which 9 were elevated fibrinogen but this was less than 1 standard deviation above norm threshold. Other findings were three patients with marginally decreased antithrombin below norm threshold, low protein S Ag in only one patient, and Factor V Leiden mutation heterozygosity in two patients, which was not higher than normal population prevalence. Thrombophilia-associated factors did not differ between sexes (p = ns) nor correlated with smoking status (p = ns).

Conclusions: Thrombophilia-associated factor abnormalities in patients with SONK were minimal. Therefore, clinical workup and treatment strategy in this disease should focus on addressing alternative etiologies leading to abnormal subchondral bone metabolism with focal osteopenia.