Fragility fractures, self-rated health and treatment with a spinal orthosis in older women in primary health care
Authors: Uzunel Elin 
Published: February 2025

<p dir="ltr">Fragility fractures, particularly hip fractures and vertebral fractures, are associated with significant morbidity, reduced functional status, and increased mortality in older adults. Identifying reliable predictors of fracture risk and mortality, as well as effective management strategies, is critical for improving outcomes in older adults. This research investigated whether self-rated health (SRH) or combined blood levels of parathyroid hormone (PTH) and insulin-like growth factor-binding protein 1 (IGFBP-1) may provide additional prognostic value. We also evaluated the effects of non-pharmacological interventions, exercise and wearing an activating spinal orthosis, on osteoporosis-related symptoms.</p><p dir="ltr">In Study I a cohort of 350 community-dwelling women aged 69-79 years (median 72.4) assessed their SRH by answering the question "How would you rate your health right now?" using a visual analogue scale (0-100 mm) at baseline. They were followed for 10 years and data on hip fractures and all-cause mortality were retrieved from healthcare registers. SRH was categorised as low, intermediate, or high (reference). Associations with the 10-year risks of hip fractures and all-cause mortality were analysed using Cox proportional hazards regression model. During the 10-year follow-up, 40 hip fractures and 72 deaths occurred. Women with low and intermediate SRH had a significantly higher risk of hip fracture (HR: 3.17, 95% CI: 1.25-8.01 and HR: 2.75, 95% CI: 1.08-7.04, respectively) compared to those with high SRH. The association remained significant after adjusting for bone mineral density. No association was observed between SRH and all-cause mortality.</p><p dir="ltr">In Study II the same cohort as in Study I was studied, but this time we investigated whether baseline blood levels of PTH in combination with IGFBP-1 were associated with a 10-year risk of hip fractures and all-cause mortality. Blood samples were collected from 338 women. Participants were divided into four groups: (A) normal PTH and low IGFBP-1, (B) normal PTH and high IGFBP-1, (C) elevated PTH and low IGFBP-1, and (D) elevated PTH and high IGFBP-1 (reference). Ten-year data on hip fractures and all-cause mortality were retrieved from healthcare registers Associations with a 10-year risks of hip fractures and all-cause mortality were analysed using age-adjusted Cox proportional hazards regression models. Women with elevated PTH and high IGFBP-1 (D) had a two- to threefold increased risk of all-cause mortality compared to the other groups. No association was found between PTH and IGFBP- 1 levels and hip fracture risk.</p><p dir="ltr">Studies III and IV are based on the same randomised controlled trial including 113 women aged >60 years with back pain and osteoporosis, with or without vertebral fractures. The participants were randomised into three groups: spinal orthosis, equipment training, and control. Assessments were performed at baseline, after 3 months and after 6 months. In Study III we analysed the difference between the three groups regarding back pain, back extensor strength, and kyphosis index. Statistical analyses were conducted using mixed models for repeated measures according to intention-to-treat (ITT) and per-protocol (PP) principles. The change in extensor strength in each group was analysed with paired t-test. In Study IV, we analysed differences between the three groups regarding health-related quality of life (HRQoL), which was measured by using the quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFFO-41) and the Short Form health survey (SF-36). Statistical analyses were conducted using mixed models for repeated measures according to ITT and PP principles. We also used Wilcoxon signed-rank test to compare HRQoL values at baseline, 3 months, and 6 months within groups and Mann-Whitney test to compare controls to intervention groups regarding change of CGRP, IL-6, and SP from baseline to 6 months.</p><p dir="ltr">A total of 96 participants completed the study. In Study III, no significant differences were observed between groups for back pain, kyphosis index, or back extensor strength after 6 months. However, back extensor strength increased within groups: 26.9% in the spinal orthosis group, 22.1% in the training group, and 9.9% in the control group. In Study IV no significant improvement in quality of life (QoL) was observed. No changes were detected in the levels of calcitonin gene-related peptide (CGRP) or substance P (SP). Interleukin-6 (IL-6) levels were significantly lower at six months in the spinal orthosis group compared to the other groups.</p><p dir="ltr">In conclusion our findings suggest that SRH may serve as an independent risk marker for hip fractures, complementing assessments based on BMD. Simultaneously elevated PTH and IGFBP-1 levels are associated with increased mortality (all-cause and cardiovascular) but not fracture risk. Non-pharmacological interventions, such as activating spinal orthoses and equipment training, may improve back extensor strength, though their impact on pain, kyphosis and HRQoL remains unclear. Spinal orthosis may be an alternative treatment method in osteoporosis, though further studies are needed.</p><h3>List of scientific papers</h3><p dir="ltr">I. <b>Uzunel E,</b> Lundin H, Wändell P, Salminen H. Association between self-rated health and the risk of hip fracture and mortality in a cohort of older women during a 10-year follow-up. Blank RD, redaktör. PLoS ONE. 05 mars 2021;16(3):e0247924.<br><a href="https://doi.org/10.1371/journal.pone.0247924" rel="noreferrer" target="_blank">https://doi.org/10.1371/journal.pone.0247924</a></p><p dir="ltr"><br></p><p dir="ltr">II. <b>Uzunel E,</b> Ranch Lundin H, Grahn Kronhed AC, Wändell P, Salminen H. Levels of parathyroid hormone and IGF binding protein 1 and associations with mortality and hip fractures in older women. Sci Rep. 26 november 2024;14(1):29399.<br><a href="https://doi.org/10.1038/s41598-024-80527-7" rel="noreferrer" target="_blank">https://doi.org/10.1038/s41598-024-80527-7</a><br><br></p><p dir="ltr">III. Kaijser Alin C, <b>Uzunel E,</b> Grahn Kronhed AC, Alinaghizadeh H, Salminen H. Effect of treatment on back pain and back extensor strength with a spinal orthosis in older women with osteoporosis: a randomized controlled trial. Arch Osteoporos. december 2019;14(1):5<br><a href="https://doi.org/10.1007/s11657-018-0555-0" rel="noreferrer" target="_blank">https://doi.org/10.1007/s11657-018-0555-0<br><br></a></p><p dir="ltr">IV. <b>Uzunel E,</b> Grahn Kronhed AC, Kajser Alin CK, Ahmed AS, Wändell P, Salminen H. The Effect of Group Training or Spinal Orthosis on Quality of Life and Potential Plasma Markers of Pain in Older Women With Osteoporosis. A Randomized Controlled Trial. Archives of Rehabilitation Research and Clinical Translation. december 2023;5(4):100297.<br><a href="https://doi.org/10.1016/j.arrct.2023.100297" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.arrct.2023.100297</a></p>