Introduction

Osteoarthritis (OA) and osteoporosis (OP) are two common age-related musculoskeletal disorders with a prevalence of 7% and 18.3%, respectively [15, 35]. Although earlier believed to be mutually exclusive [5, 16], some studies have indicated that both OA and OP are not mutually exclusive, and are common musculoskeletal disorders that could coexist in the same individual [1, 4, 12, 14]. The relationship between these two diseases remains unclear and is a subject of ongoing research. Studies focusing on the relationship between OA and bone mineral density (BMD) (indicating osteoporosis) posit that both diseases can have a direct relationship where higher BMD is observed in individuals with OA [3, 7, 18, 22, 30]. On the other hand, Foss et al. [13] as far back as 40 years ago, suggested an apparent inverse relationship between the two diseases. Similarly, other reports suggest an inverse relationship between the presence of OA and OP [10, 41].

Studies on radiographic OA of the hip and BMD showed an increase in BMD measurements taken at remote proximal and distal sites of the radius and at the calcaneus in women with severe hip OA compared to individuals without OA [17, 29]. Lingard et al. [27] submitted that a significant proportion of patients with OA have OP but that the diagnosis may be missed unless BMD measurements are performed at sites distant from the joints affected by OA. This is because OA characteristic features such as osteophyte formation and subchondral sclerosis that are presented at the joint can alter/increase the BMD measurements done by central dual-energy x-ray absorptiometry (DEXA) of the spine and hip [29]. Thus, whether there is a direct or inverse correlation between OA and OP, and whether low BMD may be a comorbidity of OA are separate questions. El Miedany et al. [12] submitted that an increase in BMD did not appear to be related to patient characteristics of body weight, age, physical activity, or medication use. Some of the clinical correlates of OA that have been documented in the literature include BMI, symptom duration, pain, function and stiffness, quality of life, etc. [33, 34]. Considering the possible interrelationship between OA and OP, clinical measures directed at ameliorating OA symptoms may improve BMD, and this might be an important therapeutic pathway. This systematic review seeks to synthesize the current evidence and offer direction on the knee OA-OP nexus to provide clinical care guidelines.

Methods

The Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) [31] and the protocol defined by the Joanna Briggs Institute (JBI) Methodology for Systematic Reviews were followed in this review. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022334000).

Study selection criteria

Population, exposure, study types, settings, and outcomes

The population of interest of this review was male and female adults (≥ 40 years) diagnosed with hip and/or knee OA using the American College of Rheumatology Criteria (ACR), KL system of classification, doctor diagnosis, and Ahlback grading scale. Studies with general rheumatic and osteoarthritis conditions were considered only if subgroup results for hip and knee OA were presented. Studies that assessed BMD (either reported as BMD, osteopenia, or osteoporosis) at sites including the spine, femur, total hip, and /or a combination of these sites in individuals with hip and/or knee OA were included. We included all types of observational studies, i.e., cohort, case–control, and cross-sectional studies from all settings. All clinical outcomes reported in eligible studies were identified and included.

Eligibility criteria

Inclusion and exclusion criteria

Peer-reviewed studies that included a knee and/or hip OA population or sub-sample of knee and/or hip OA diagnosed using radiographic evidence and/or clinical diagnosis (as defined by the American College of Rheumatology criteria) [2] or according to Kellgren Lawrence (KL) grading [23] and that assessed the BMD as a measure of Osteoporosis.

According to the World Health Organization [39], OP was defined as a BMD T-score at the hip and/ or the spine of < 2.5 standard deviations (SD) for postmenopausal women, and T-scores of between − 1 and − 2.5 SD for men and women over the age of 50 years [21, 28]. Gray literature, abstracts, protocols, or non-human studies with a mixed population of OA without a subgroup analysis for hip and or knee OA and non-English were excluded.

Search strategy

Online electronic databases of CINAHL, Cochrane, Medline, PsycINFO, Pubmed, Web of Science, and African Journal (from inception to September 12, 2022). The initial keywords used in the review were “bone mineral density” OR “bone density” OR “Osteoporosis” OR “Osteopenia” OR “fracture”; “risk factors” OR “outcomes” OR “correlates” OR “Prevalence”; and “Knee osteoarthritis” OR “hip osteoarthritis”. The complete search strategy implemented is presented in Supplementary material (see Appendix). Also, the reference list of included studies and two related systematic reviews were screened to extract related articles. Eligible study design included prospective longitudinal cohort, cross-sectional, and case studies.

Screening and selection of studies

Duplicate citations were eliminated by one of the authors (BAA). In the first phase, three independent assessors (IO, HF, and OO) screened the titles and abstracts of the articles returned by the search. BAA arbitrated the searches of the two assessors where there were contentions on the inclusion/exclusion of articles. In the second phase, full-text manuscripts of possibly eligible studies were retrieved and reviewed by each of the independent assessors using a standardized Microsoft Excel screening spreadsheet to identify relevant studies. Data were extracted on study setting, study population, sample size, study design, measures of BMD and OA used, statistical analysis, and main findings. To ensure quality control of data extraction, both virtual and physical meetings were held among the assessors (IO, HF, and OO) and the third reviewer (BAA) to discuss cases.

Quality assessment of selected studies

Assessment of reporting quality and the risk of bias for each paper was done using the Joanna Brigg’s Institute (JBI) Critical Assessment tool which is a widely used and recommended assessment tool by Cochrane for evaluating qualities of observational and cross-sectional and case–control studies. The tool for observational and cross-sectional studies comprises 8 items (all applicable to cross-sectional studies) while that for case–control studies comprise 10 items. The quality assessment for each included study was carried out by two independent assessors (OI and HO) using the scoring system of yes (Y), No (N), Unclear (U), or not applicable (NA). An arbitrator (BAA) acted as a tie-breaker whenever a consensus could not be reached.

Data synthesis

Meta-analysis was not performed due to the high heterogeneity levels with regard to study designs and methodology. However, findings were presented using a narrative synthesis to report the association between clinical factors of hip and/or knee OA and BMD. Further, we performed the best evidence synthesis of clinical factors that were investigated in two or more studies and ranked evidence grading based on previous studies [38, 40] to grade the level of evidence supporting the association (see Appendix). We classified studies according to study design, with the preferred being cohort study followed by case–control design, and lastly cross-sectional design. Studies were ranked according to their methodological quality score. Identified clinical factors were classified in the direction and strength of association by using correlation or standardized coefficient as weak (< 0.3), moderate (> 0.3 < 0.7), and strong (≥ 0.7) [19] or with odds ratio [9] where these were reported. We adjudged results as consistent if BMD was significantly associated with the identified clinical factor of OA in the same direction of the association.

Results

Literature search and study selection

Three thousand, three hundred and fifty-five (3355) articles were identified through database searches, and 3 articles were identified through a review of the reference lists of relevant papers and a hand search. Of these articles, we removed 1751 duplicates. The titles and abstracts of the 1604 remaining articles were screened, and of these, 25 full papers were accessed for further review of eligibility. Twenty-one articles were excluded and the remaining 5 articles ((3 cross-sectional studies [11, 27, 37] and 2 case–control studies [8, 32])) The PRISMA flow diagram on the search strategy results of this review is shown in Fig. 1.

Fig. 1
figure 1

PRISMA flow diagram (source— [31])

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Study characteristics and association between BMD and OA clinical factors

Extracted data included data for 1295 participants. All five studies were completed in different countries, viz; Germany [11], Korea [8], UK [27], China [37], and Poland [32]. Two of the studies [11, 27]) had more female than male participants, while 3 recruited only female participants [8, 32, 37]. Furthermore, one of the studies specifically recruited only post-menopausal women [32].

Three of the studies [8, 11, 37] diagnosed BMD using Kellgren-Lawrence (KL) scores. One study [27] only required a doctor’s diagnosis while the final study [32] made use of the American College of Rheumatology (ACR) clinical classification criteria for Knee OA.

Clinical factors assessed by the studies were: BMI [11, 27, 32, 37],pain, function, and stiffness [8, 27],symptom duration [37],presence of varus/valgus deformity [37],quality of life [8],and knee function [8]. Tables 1 and 2 show the summary of all the studies included in the review.

Table 1 Summary of the included studies
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Table 2 Summary of the included studies
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Results across four studies showed BMI to be an important clinical factor associated with BMD among people with osteoarthritis [11, 27, 32, 37]. Pain, function, and stiffness [8], female gender [27], varus deformity [37], QoL-physical component [8], and knee function [8] were all also significantly associated with BMD.

However, mental component summary QoL [8], symptom duration [37], valgus deformity [37], and incidence of bilateral KOA [37], did not demonstrate significant associations with BMD among the population.

Quality assessment

Three (3 cross-sectional studies [11, 27, 37], and two case–control studies [8, 32] were rated as having good quality and included in the review. The summary of the quality assessment is presented in Tables 3 and 4.

Table 3 JBI critical appraisal checklist for analytical cross-sectional studies
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Table 4 JBI critical appraisal checklist for case–control studies
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Best evidence synthesis

Following the best evidence synthesis, there was limited evidence to support the association between BMD measured at any site of the body and BMI. In addition, there was a conflicting evidence for the association of BMD with age and gender. When BMD was measured at the lumbar spine, the evidence for the association between BMD and BMI became conflicting. For other identified clinical factors, there was insufficient evidence to support an association with BMD. Strengths of association and levels of best evidence are summarized in Tables 5 and 6, respectively.

Table 5 Strength of association between Bone Mineral Density and identified clinical factors
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Table 6 Overview and best evidence synthesis regarding the association between clinical factors of hip and /or knee osteoarthritis and poor bone mineral density
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Discussion

This systematic review aimed to summarize current epidemiological evidence on the association between BMD and clinical factors of hip and/or knee OA. Due to high heterogeneity levels in study designs and limited number of studies, the review employed a narrative and best evidence synthesis, which enabled grading of factors into different levels of evidence. There were five studies that evaluated the association of BMI with BMD, with majority having longitudinal design. The best evidence synthesis found limited evidence for the positive association between low BMI and poor BMD measured at any site of the body. Conflicting evidence was found for the association between BMD and each of age and gender. When BMD was measured at the lumbar spine, the evidence for the association between BMD and BMI became conflicting. All other factors identified had insufficient evidence. From the table above, all the studies reviewed were from Europe and Asia. No study was found from Africa or America. Furthermore, most of the reviewed studies recruited knee OA alone and only one recruited patients with hip and knee OA [27].

The association between bone mineral density and OA has long been a subject of debate in the literature [18, 36]. Although the exact pathophysiology remains unclear, this association between OA and OP has been known from early cross-sectional studies [6, 20, 26, 33]. Bone is considered an integral structure in the pathogenesis of OA and the role of local and systemic bone mineral density (BMD) is gaining increasing interest [33]. A relatively recent review demonstrated the similarities in etiology, risk factors, and shared mechanisms between BMD and OA, which suggests a possible association with clinical factors of OA like BMI [14]. It is important to note that high BMI may be protective of BMD especially in among males and black populations populations [25]. However, excessive BMI may be harmful to BMD as Li [25] reported an inverted U-shaped association between BMD and BMI. More studies are needed to understand these associations among the blacks and especially in the African population. Longitudinal BMD loss has been reported to be associated with progressive cartilage loss in knees with OA Patients thus suggesting that severity of knee OA may be directly related to the BMD of the individual [24]. With the advent of therapies that modify bone turnover, a better understanding of the relationship between BMD and structural/ clinical changes in knee OA may have important implications for important clinical outcomes of the disease like,onset and/or progression [24].

There was considerable variation in the assessment sites for BMD in the studies. The studies by some of the authors [8, 11] had BMD measurements made at the proximal femur and lumbar spines in their studies. In one study [37], BMD was assessed at the proximal femur, femoral neck and lumbar spines. In the fifth study [32], BMD assessment was done at the proximal femur and lumbar spine. Lingard et al. [27] who made measurements at the forearm in addition to the spine and proximal femur, reported significant proportion of patients with severe OA had low BMD and that the diagnosis may be missed unless BMD measurements are performed at sites distant from the joints affected by OA.

Implications for clinical practice

Clinicians should potentially target increased BMI, especially by strengthening skeletal muscles which may improve BMD of patients with osteoporosis and osteopenia in the long run. In addition, an increase in BMI may promote mechanical stress on the body density, subsequently improving BMD.

Implications for further research

Well-conducted longitudinal studies with adequate sample sizes and diverse OA populations are needed as this would provide more comprehensive understanding of the association between clinical factors and BMD in osteoarthritis. In addition, it is important to investigate clinical factors associated with BMD in other climes such as Africa and America as environmental factors may influence the perpetuation and presentation of OA. Further, future studies may consider other potentially relevant factors that may be associated with BMD, including: medication use, physical activity levels, sedentary behavior patterns, and dietary habits.

Strengths and limitations

This study is the first to investigate the association between BMD and clinical factors of hip and or knee OA. In addition, we used best evidence synthesis to adjudge the current level of evidence for the association. This study is however with limitations. These study findings were based on only five studies a higher proportion of which were cross-sectional designs, limiting the ability to draw robust conclusions. As noted by one of the studies the variability of assessment sites might influence BMD detection [27]. The use of convenience sampling techniques would also negatively impact the internal validity of these studies. In addition, our search might have missed some studies published in non-English journals, thus, other clinical factors might not have been identified.

Conclusion

This systematic review synthesizes current evidence on BMD and its associated clinical factors. High likelihood of bias and limited evidence at best suggests a need for well-designed studies on the relationship between OA and BMD.