One leg standing time predicts fracture risk in older women independent of clinical risk factors and BMD

The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study, carried out in the greater Gothenburg area. Women were chosen randomly from the Swedish national population register and asked to participate through invitation letters. In total, 6832 women were initially contacted, of which 436 (6.4%) were excluded for reasons including bilateral hip replacement, inability to communicate in Swedish, or not being able to walk with or without a walking aid. Of all women contacted who met the inclusion criteria, 3368 (52.6%) declined to participate, resulting in an inclusion rate of 47.4% [32]. Thus, the final SUPERB study cohort comprised 3028 women, 75–80 years old. All subjects signed an informed consent, prior to participation and the study has been approved by the Swedish Ethical Review Authority. The criteria for invitation to the study center, Department of Geriatrics, Sahlgrenska University Hospital Mölndal, Sweden, were as follows: (1) acceptance of the invitation sent by letter and giving a positive response of the follow-up telephone call, (2) availability to attend a clinic visit, (3) being ambulatory, (4) being able to understand Swedish, (5) being a woman between the age of 75 and 80.

A wall-mounted calibrated stadiometer was used to measure body height. Balance was measured by the clinical balance test OLST [33]. The OLST was performed with the tested participant not wearing shoes, standing on one leg with the other leg bending backwards at the knee, with arms crossed over the chest, and with eyes open. After a practice session, the test was performed twice for each leg. The test was stopped if the elevated leg touched the floor, if the position of the arms was changed, or if the foot standing on changed position. The average of the best result for either leg was used as the exposure. In total, 623 women declined to perform the test, resulting in an available OLST in 2405 women.

The questionnaires had two parts, comprising a self-completed form and a form completed in discussion with the research nurse. The questionnaire covered eight different domains, including medical and fracture history, use of medication, current smoking, occurrence of falls in the last 12 months, alcohol consumption, and parental hip fracture. Information regarding physical activity and self-reported quality of life were collected using the 12-Item Short-Form Health Survey (SF-12), yielding a physical (PCS) and mental summary (MSC) score [34]. Physical activity habits were investigated with the Physical Activity Scale for the Elderly (PASE) [35] survey.

Dual-energy X-ray absorptiometry (DXA) was used for assessment of bone mineral density (BMD) and body composition. The locations of BMD measurements were the lumbar spine (L1–L4), the femoral neck, and the total hip. A total body scan was used in order to estimate the amount of fat and lean body mass. The coefficients of variation (CVs), at our facility, were 0.7% for lumbar spine BMD, 0.8% for total hip BMD, and 1.3% for femoral neck BMD, for women aged 75–80. The DXA machine used for assessment was a Hologic Discovery A device (Hologic, Waltham, MA, USA).

A regional digital X-ray archive including all the 49 municipalities in the Västra Götaland region surrounding Gothenburg was used to retrieve the images and/or X-ray reports. All fractures were recorded and were subsequently categorized as major osteoporotic fracture (MOF), nonvertebral fracture, and hip fracture. MOF comprised fractures of the spine, hip, forearm, and proximal humerus. Skull, face, hand, and foot fractures were excluded from nonvertebral fractures. All the radiology reports were reviewed by research nurses and a physician. This assessment was carried out from the baseline exam (March 2013 to April 2016) until May 24, 2018. Identified radiographs without an available radiology report or a report without a specified fracture diagnosis were reviewed by an experienced orthopedic surgeon.

All statistical analyses were conducted via SPSS Statistics version 24 (IBM Corporation, Armonk, NY, USA) or STATA 16.0 (StataCorp, College Station, TX, USA). For continuous variables, independent samples t-tests were used to examine differences between groups. χ² and Fisher’s exact tests were used for dichotomous variables. The association between OLST as a continuous variable and the risk of fracture was examined using an extension of the Poisson regression model [36, 37] in the whole cohort. The observation period of each participant was divided in intervals of 1 month. The first fracture per person was counted for each relevant outcome. Covariates included current age and time since start of follow-up. A spline Poisson regression model was fitted using cohort-specific knots at the 10^th, 50^th, and 80^th percentiles of OLST, corresponding to OLST 2.94 s, 11.48 s, and 24.58 s, in order to study the association between OLST and fracture risk in more detail. The splines were second-order functions between the breakpoints and linear functions at the tails resulting in a smooth curve. A p-value less than 0.05 was considered significant. Since no apparent threshold in the relationship was seen, particularly for hip fracture, the previously proposed 10-s [30, 38, 39] threshold was applied to identify a high-risk group. Cox proportional hazard models were also used to study associations between OLST (OLST <10 s or ≥10 s) mortality and incident fractures. The models were adjusted for age, height, and weight as well as additional covariates, as specified in Table 2. Hazard ratios (HR) and 95% confidence intervals obtained from Cox models are presented. To assess death as a competing risk for osteoporotic fractures, Fine and Gray’s hazard function was used [40]. Hazard functions for fracture and death were used to calculate 4-year and 10-year probabilities.

The mean age of included women was 77.7±1.6 years at baseline (mean ± SD) and the follow-up time was 3.6 (1.5) years (median, interquartile range (IQR)). During follow-up, 82 women died and 238 major osteoporotic fractures, 44 hip fractures, and 228 nonvertebral fractures were observed in the investigated cohort. Women who declined to take the OLST had a greater BMI, were less physically active, and had higher prevalence of previous falls, fractures, and of most comorbidities than women who performed the OLST (Supplemental Table 1a).

The relationship between OLST, incident major osteoporotic fractures, and hip fracture showed a steady increase in fracture risk with declining OLST (Fig. 1a, b). The included participants were divided into two groups, OLST <10 s (n=1094) and OLST ≥10 s (n=1311). Characteristics of women with OLST <10 s and women with OLST ≥10 s at baseline are presented in Table 1. Women with OLST <10 s were slightly older, weighed more, and had higher body mass index (BMI) than women with higher OLST (Table 1). In addition, an OLST <10 s was also associated with slightly higher lumbar spine BMD, while no differences in hip BMD or FRAX scores (with the exception of a slightly higher FRAX MOF score for those with low OLST) were observed between the low and high OLST groups.

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Women with low OLST had higher prevalence of fall accidents during the last year, but not of prevalent fractures than those with higher OLST (Table 1). Furthermore, low OLST was associated with higher frequencies of smoking and excessive alcohol consumption as well as with higher prevalence of several diseases or conditions, including chronic heart failure, type 2 diabetes, myocardial infarction, chronic bronchitis, asthma, or emphysema, reflecting increased frailty (Table 1).

The incidence of nonvertebral fracture, major osteoporotic fracture, and hip fracture was higher in women with OLST <10 s than in women with OLST ≥10 s. With adjustment for age, height, and weight, a Cox proportional hazard model revealed that OLST <10 s (vs. ≥10 s) was associated with 61% increased risk of nonvertebral fracture (hazard ratio (HR) and 95% confidence interval (CI) 1.61 [1.27–2.06]), 76% increased risk of major osteoporotic fractures (HR, 95% CI 1.76 [1.34–2.30]), and 3 times increased risk of hip fracture (HR, 95% CI 3.02 [1.50–6.10]). OLST was associated with all fracture outcomes also after adjustments for the FRAX clinical risk factors (previous fracture, family history of hip fracture, current smoking, oral glucocorticoid use, rheumatoid arthritis, excessive alcohol intake), osteoporosis medication, and history of falls both in models with and without femoral neck BMD included (Table 2). In total, 4.8% of women with a low OLST died during follow-up, compared to 2.2% in women with longer OLST, corresponding to an 82% increased risk of death (Table 2).

The 4-year probabilities of major osteoporotic fracture for women at age 75 or 80 years old, without previous fracture, BMI of 26 kg/m², and no additional clinical risk factors, were also calculated according to femoral neck BMD T-score, with or without consideration to OLST (< 10 s or ≥10 s) in the analysis. For a 75-year-old woman with BMD T-score −2, OLST < 10 s was associated with a higher 4-year probability (12.5% vs. 8.0%). The corresponding 4-year probability for an 80-year-old woman with a T-score of −2 was 12.0% and 7.7% for OLST (<10 s or ≥10 s), respectively (Fig. 2a, b). The ratios between the calculated 4-year probability without considering OLST and with OLST <10 s for women 75 and 80 years old, without previous fracture, BMI of 26 kg/m² and no other clinical risk factors, according to femoral neck BMD T-score are presented in Fig. 3. The relative importance on fracture probability of having OLST < 10 s was slightly greater at higher BMD in both 75- and 80-year-old women. Study subject follow-up time was then extrapolated up to 10 years to allow for calculations of 10-year fracture probability. The 10-year probabilities of major osteoporotic fracture for women 75 and 80 years old were calculated, setting BMI to 26 kg/m², and all clinical risk factors set to no, according to femoral neck BMD T-score, with or without consideration to OLST (< 10 s or ≥10 s) in the analysis. For a 75-year-old woman with BMD T-score −2, a low OLST < 10 s increased the 10-year probability substantially, from 21.1 to 30.6%. The equivalent 10-year probability for an 80-year-old woman with a T-score of −2 was 19.7% and 28.0%, for OLST ≥10 s or <10 s, respectively (Fig. 2c, d). The impact of OLST on 10-year fracture probabilities according to age and BMD is presented in Appendix Table 1b, c.

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The association between OLST <10 s and risk for major osteoporotic fracture (subhazard ratio (SHR) and 95% CI: 1.56 (1.18–2.06)), hip fracture (SHR 2.37 (1.13–4.96)), and nonvertebral fracture (SHR 1.41 (1.06–1.86)) did not change substantially when a competing risk survival regression model, adjusted for age, height, and weight, was applied.