Assessment of bone metabolism and quality of life in knee osteoarthritis patients with low bone mineral density

Abstract

Purpose: Osteoarthritis (OA) and Osteoporosis (OP) are two respective diseases in skeletal system correlated with aging. They are different diseases but often coexist in one patient. The relationship between them is complicated and controversial. With the update of OA definition, a new conception called “Bone-driven OA subtype” was put forward, suggesting that abnormal bone metabolism plays a key role in OA development. OA complicated with OP may be a separate subtype of OA, with its own features different from neither OA nor OP. However, the underlying researches on this subtype are still sparse. The current cross-sectional study was conducted by recruiting people aged between 40∼80 years old to: (i) investigate the prevalence and risk factors of OA patients complicated with low BMD; (ii) assess their bone metabolism status; (iii) evaluate their general health status. Methods: The study was conducted in accordance with the World Medical Association Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects. All participants provided written informed consent to participate in this research, which was approved by the Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University (the approval number of ethics is KYLLSL-2018-231). Physical examination of knee joints was performed. To measure the degree of functional impairment and to identify the severity of disease in patients with KOA, we included Western Ontario questionnaire and the McMaster Universities Osteoarthritis Index (WOMAC)as well as SF-36. The free and informed consent, as well as a questionnaire were applied by the researcher. Bone mineral density (BMD) of the lumbar spine and bilateral proximal femora was performed by a Dual Energy X-Ray Absorptiometry (DEXA) machine. Blood samples were collected and laboratory tests performed for detection of bone turn-over markers (β-CrossLaps, PINP and N-MID Osteocalcin N). Radiographs in AP+P load of bilateral knees were evaluated and a radiological classification was performed by two independent observers using the Kellgren-Lawrence (KL) scores. Data were expressed as means ± standard deviations for continuous variables and as numbers and percentages for categorical data. The Student t-test, one-way ANOVA test and the chi-square test were used. Significance value was p<0.05 at 95% confidence interval. Results: Prevalence of KOA with low BMD 956 subjects were enrolled. There were 164 (17.15%) KOA patients complicated with low BMD, accounting for 72.25% of KOA patients. Their mean age was 57.70±7.68 years, and mean BMI was 25.00±2.98 kg/m2. When stratified with age and gender, the prevalence elevated along with age and was significantly higher in menopausal women (72.9%, P<0.001) (Table 1). There was a trend that the prevalence of KL scores ≥2 (28.7%, n=47) in these patients was higher than that (22.2%, n=14) in KOA with normal BMD group. BMD and Serum bone turnover markers in KOA with low BMD The serum levels of bone formation markers (ALP, PINP and N-MID Osteocalcin) and bone absorption markers (β-CrossLaps) in KOA with low BMD patients were significantly higher than that in KOA with normal BMD group and healthy control group (P<0.001) (Table 1). Mean BMD and T-scores at lumbar, femoral neck and total hip of these patients were significantly lower than that in KOA with normal BMD group and healthy control group (p<0.001). There also appeared to be an inverse relationship between severity of KOA and mean BMD at total hip and femoral neck (Fig. 1). General health status in KOA with low BMD Evaluated with SF-36, mean values of all the dimensions reflecting body health and mental health (except for MH) in KOA with low BMD patients were significantly lower than that in OP and healthy control group (P<0.05). Conclusions: OA is a heterogenous disease with a variety of pathophysiologic drivers leading to multiple phenotypes. Bone-driven OA is a specific subtype that associated with OP and osteopenia, characterized as active bone turnover rate caused by local or systemic abnormal bone metabolism in early stage of OA. For these patients, low BMD is a risk factor of OA development. Evaluation of health outcome by SF-36 showed that both body health and mental health of these patients had severely suffered. Therefore, this subtype will progress rapidly and present specific bone metabolism features. Our findings shed new light on patient stratification and the development of precision medicines for OA. New and effective approaches have to be developed to focus on abnormal bone metabolism in the treatment of Bone-driven OA.