Two authors (AS, SU) independently searched published studies indexed in the MEDLINE, EMBASE, and LILACS (Literatura Latino Americana em Ciências da Saúde) from their date of inception to November 2015. References of all selected studies were also examined. The following main search terms were used: osteoporosis, osteopenia, bone density, bone mass, bone loss, hearing loss, audiometry, otoacoustic. The full search strategy was detailed in Appendix 1.

Articles were considered eligible for inclusion if the following criteria were met: (1) published observational studies including cross-sectional, cohort, and case–control studies; (2) study in adults age 18 years or older; (3) clear methods of assessment of bone mineral density and hearing status were described; (4) clear diagnostic criteria for osteoporosis and hearing loss were reported; and (5) association of low BMD or osteoporosis and hearing loss was reported as either adjusted or unadjusted hazard ratios (HRs), relative risks (RRs), or odds ratios (ORs) with associated 95% confidence intervals (CIs), or hearing sensitivity in decibels. Exclusion criteria were (1) reviews, case reports, abstracts, and unpublished studies, (2) studies without specific sample origins, (3) data in the study was not presented clearly enough, and (4) participants with known otosclerosis.

Osteoporosis was defined as having a bone mineral density (BMD) with a T-score of less than −2.5 SD as measured by dual-energy X-ray absorptiometry or other standard technique at anatomical bone sites including lumbar spine, femoral neck, and total hip. The main outcome of this study was hearing loss as assessed by audiometry or self-reported assessment. We used the definition of hearing loss (conductive, sensorineural, or mixed) as described by each study.

Two authors (AS and SU) independently reviewed titles and abstracts of all citations that were identified. After all abstracts were reviewed, data comparisons between the two investigators were conducted to ensure completeness and reliability. The inclusion criteria were independently applied to all identified studies. Differing decisions were resolved by consensus.

Full-text versions of potentially relevant papers identified in the initial screening were retrieved. If multiple articles from the same study were found, only the article with the most complete data was included. Data concerning study design, participant characteristics, source of data, comorbidities, methods of assessing BMD and hearing impairment, outcome assessment, and factors adjusted in multivariable analysis were independently extracted.

A subjective assessment of methodological quality for observational studies was evaluated by two authors (AS and SU) using the Newcastle–Ottawa Scale (NOS). The NOS is a quality assessment tool for non-randomized studies. The NOS includes eight items, categorized into three dimensions of selection, comparability, and outcome. For each dimension, a list of response options is provided. Scoring is based on a semi-quantitative assessment of study quality. The highest quality studies are scored a maximum of one point for each item. However, there is an exception of the item related to comparability that allows the assignment of two points. The range of NOS is between zero up to nine points.15 A total score of 3 or less was considered poor, 4–6 was considered moderate, and 7–9 was deemed high quality. We excluded studies from our meta-analysis if they had poor quality. Discrepant opinions between authors were resolved by consensus.

We performed meta-analysis of the included studies using Comprehensive Meta-Analysis 3.3 software from Biostat, Inc. We used a random-effects model if there was high heterogeneity (I2>50%) and fixed-effects model if there was low heterogeneity (I2<50%). We calculated pooled HR, RR, or OR of hearing loss with 95% confidence intervals (CI) comparing between participants with normal BMD and with low BMD or osteoporosis at each anatomical site and with any anatomical sites. We also calculated pooled mean difference (MD) with 95% CI of hearing sensitivity in each frequency comparing between the normal BMD group and the low BMD group. We excluded studies from meta-analysis and only presented the result with narrative description when there were not sufficient comparable data available for outcome of interest. The heterogeneity of effect size estimates across these studies was quantified using the Q statistic, its p-value, and I2 (p<0.10 was considered significant). Subgroup analysis by site of BMD was performed to find the source of heterogeneity. Publication bias was assessed using funnel plot and Egger's regression test.

The initial search yielded 83 articles (Fig. 1); 67 articles were excluded because they were not original observational studies (23 articles), did not have BMD data (12 articles), did not have hearing loss data (6 articles), or did not measure association between BMD and hearing loss (26 articles). A total of 16 articles underwent full-length review. Data were extracted from eight studies involving 52,828 participants who had bone mineral density and hearing status assessed.2,12,13,16–20

Figure 1.

Results of information search.

(0.21MB).

Most of them had cross-sectional design; others were prospective cohort, retrospective cohort, and case–control studies. Included studies were from Turkey, USA, and Korea. These included national population-based studies from two nations. All participants were assessed by bone mineral density by standardized methods (dual energy X-ray absorptiometry or DXA). Sites of BMD measurement were femur, lumbar spine, head, and methods of assessing hearing status included audiometry, otoscopic examination, and self-reported. The characteristics of the eight extracted studies included in this review are outlined in Table 1.

The quality of nine cross-sectional, three cohort and, two case–control studies were evaluated by NOS (Table 1). Total score ranged from 3 to 8. Two studies had low quality (total score=3) and were exclude from the meta-analysis.

Five studies (2, 12, 13, 16, 20) were included in the meta-analysis of hearing loss. There was a statistically significant increased odds of hearing loss in the low BMD or osteoporosis group with OR of 1.20 (95% CI 1.01–1.42, p=0.04, I2=82%, Pheterogeneity=0.01) (Fig. 2). The study from Clark et al., Kahveci et al., Mendy et al., and Yeh et al. all reported significantly increased odds of hearing loss in the low BMD group with OR of 1.90 (95% CI 1.37–2.63, p<0.01), 4.50 (95% CI 1.82–11.13, p<0.01), 2.08 (95% CI 1.33–3.24, p<0.01), and 1.76 (95% CI 1.33–2.33, p<0.01), respectively. However, the study from Helzner et al. reported significantly increased odds of hearing loss in the low BMD group, in particular the area and population included the femoral neck of black men 1.37 (95% CI 1.07–1.76, p=0.01) and total hip of black men 1.36 (95% CI 1.05–1.76, p=0.02).

Figure 2.

Forest plot of studies comparing odds of hearing loss in patients who had low bone mineral density or osteoporosis and control. A diamond data marker represents the overall odds ratios and its 95% CI.

(0.28MB).

To assess the stability of the results of the meta-analysis, we conducted a sensitivity analysis by excluding one study at a time. None of the results was significantly altered, indicating that our results were robust.

To investigate potential publication bias, we examined the contour-enhanced funnel plot of the included studies in assessing change in log OR of hearing loss (Fig. 3). The vertical axis represents study size (standard error) while the horizontal axis represents effect size (log odds ratio). From this plot, bias is not present because there is symmetrical distribution of studies on both sides of the mean. The Egger's test was non-significant (p=0.36). Using the trim and fill methods in the random-effects model, there was no difference of the imputed OR (1.38) and its 95% CI (1.08–1.7).

Figure 3.

Funnel plot assessing publication bias.

(0.07MB).