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Summary Frailty reflects an accelerated health decline. Frailty is a consequence of fracture and contributes to fracture. Greater frailty was associated with higher fracture risk. Frail women were at immediate risk (within 24 months) of a hip or major fracture. Fracture prevention could be improved by considering frailty status. Introduction Frailty encompasses the functional decline in multiple systems, particularly the musculoskeletal system. Frailty can be a consequence of and contribute to fracture, leading to a cycle of further fractures and greater frailty. This study investigates this association, specifically time frames for risk, associated fracture types, and how grade of frailty affects risk. Methods The study is performed in the OPRA cohort of 1044, 75-year-old women. A frailty index was created at baseline and 5 and 10 years. Women were categorized as frail or nonfrail and in quartiles (Q1 least frail; Q4 most frail). Fracture risk was assessed over short (1 and 2 years) and long terms (5 and 10 years). Fracture risk was defined for any fracture, major osteoporotic fractures (MOFs), and hip and vertebral fracture, using models including bone mineral density (BMD) and death as a competing risk. Results For women aged 75, frailty was associated with higher risk of fracture within 2 years (Hip SHRadj. 3.16 (1.34–7.47)) and MOF (2 years SHRadj. 1.88 (1.12–3.16)). The increased risk continued for up to 5 years (Hip SHRadj. 2.02 (1.07–3.82)); (MOF SHRadj. 1.43 (0.99–2.05)). Grade of frailty was associated with increased 10-year probability of fracture (p = 0.03). Frailty predicted fracture independently of BMD. For women aged 80, frailty was similarly associated with fracture. Conclusion Frail elderly women are at immediate risk of fracture, regardless of bone density and continue to be at risk over subsequent years compared to identically aged nonfrail women. Incorporating regular frailty assessment into fracture management could improve identification of women at high fracture risk. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-021-05886-7.

Summary Reduced kidney function is associated with an increased fracture risk, although the relationship between an age-related decline and fractures needs further investigation. We followed kidney function and fracture risk for 10 years. A mild-moderate decline in kidney function was associated with fracture, but not in advanced age. Introduction With age, kidney function declines. Though well known that chronic kidney disease is associated with increased fracture risk, the extent to which the typical age-related decline contributes is unclear. In the OPRA cohort, a longitudinal study of older non-selected women, we investigated the association between kidney function and fracture. Methods Cystatin C–based kidney function estimates were available at age 75 (n = 981) and 80 (n = 685). Women were categorized by kidney function: normal (CKD stages 1 and 2), mild-moderate (3a), poor (3b-5), and imminent, short- and long-term fracture risk investigated. BMD measurements and kidney function for risk prediction were also evaluated; women were categorized by both reduced kidney function (stages 3–5) and osteoporosis status. Results In the short term, 2–3 years, mild-moderate kidney dysfunction was associated with the highest risk increase: osteoporotic fractures (2 years HRadj 2.21, 95% CI 1.27–3.87) and also up to 5 years (between 75 and 80 years) (HRadj 1.51, 1.04–2.18). Hip fracture risk was similarly increased. This association was not observed from age 80 nor for women with poorest kidney function. Reduced kidney function was associated with higher risk even without osteoporosis (osteoporotic fracture; HRadj 1.66, 1.08–2.54); risk increased by having both osteoporosis and reduced function (HRadj 2.53, 1.52–4.23). Conclusion Older women with mild-moderate reduction of kidney function are at increased risk of fractures, but not those with the worst function. Our findings furthermore confirm the value of osteoporosis assessment and it is possible that in this age group, age-related decline of kidney function has limited contribution compared with BMD. Electronic supplementary material The online version of this article (10.1007/s00198-019-05152-x) contains supplementary material, which is available to authorized users.

Summary In community dwelling, 75-year-old women followed 10 years, a frailty index was created at each of three visits. Frailty score increased by ~ 6–7% annually. A higher frailty score was equivalent to being 5–10 years chronologically older. Frailty was associated with low bone density and higher risk of dying. Introduction To understand the distribution of frailty among a population-based sample of older community-dwelling women, progression over 10 years, and association with mortality and osteoporosis. Methods The study is performed in a cohort designed to investigate osteoporosis. The OPRA cohort consists of 75-year-old women, n = 1044 at baseline, and follow-up at age 80 and 85. A frailty index (scored from 0.0–1.0) based on deficits in health across multiple domains was created at all time-points; outcomes were mortality up to 15 years and femoral neck bone density. Results At baseline, the proportion least frail, i.e., most robust (FI 0.0–0.1) constituted 48%, dropping to 25 and 14% at age 80 and 85. On average, over 10 years, the annual linear frailty score progression was approximately 6–7%. Among the least frail, 11% remained robust over 10 years. A higher frailty score was equivalent to being 5 to 10 years older. Mortality was substantially higher in the highest quartile compared to the lowest based on baseline frailty score; after 10 years, 48.7% had died vs 17.2% (p = 1.7 × 10−14). Mortality risk over the first 5 years was highest in the frailest (Q4 vs Q1; HRunadj 3.26 [1.86–5.73]; p

Summary This longitudinal study investigates the association between C-reactive protein (CRP), osteoporosis, fractures, and mortality in 1044 elderly women. CRP was not an indi- cator for low bone mineral density (BMD), bone loss, or fracture in elderly women; however, women with elevated CRP levels over a prolonged period lost more bone over the 10-year follow-up, although fracture risk was not increased. Introduction Inflammation may contribute to the pathophys- iology underlying impaired bone metabolism. This study in- vestigates the association between CRP, BMD, bone loss, fracture risk, and mortality in women aged 75 and above. Methods This longitudinal study is based on 1044 women, all age 75 at inclusion, reassessed at ages 80 and 85, with a mean follow-up time of 11.6 years (maximum 16.9 years). Results Women in the lowest CRP quartile (mean 0.63 mg/L) had lower BMD compared to those in the highest CRP quar- tile(mean5.74mg/L) attotalhip(TH)(0.809vs.0.871g/cm 2 , p

In community dwelling, 75-year-old women followed 10 years, a frailty index was created at each of three visits. Frailty score increased by ~ 6-7% annually. A higher frailty score was equivalent to being 5-10 years chronologically older. Frailty was associated with low bone density and higher risk of dying.To understand the distribution of frailty among a population-based sample of older community-dwelling women, progression over 10 years, and association with mortality and osteoporosis.The study is performed in a cohort designed to investigate osteoporosis. The OPRA cohort consists of 75-year-old women, n = 1044 at baseline, and follow-up at age 80 and 85. A frailty index (scored from 0.0-1.0) based on deficits in health across multiple domains was created at all time-points; outcomes were mortality up to 15 years and femoral neck bone density.At baseline, the proportion least frail, i.e., most robust (FI 0.0-0.1) constituted 48%, dropping to 25 and 14% at age 80 and 85. On average, over 10 years, the annual linear frailty score progression was approximately 6-7%. Among the least frail, 11% remained robust over 10 years. A higher frailty score was equivalent to being 5 to 10 years older. Mortality was substantially higher in the highest quartile compared to the lowest based on baseline frailty score; after 10 years, 48.7% had died vs 17.2% (p = 1.7 × 10The frailty index was highly predictive of mortality showing a threefold increased risk of death in the frailest both in a shorter and longer perspective. Only one in ten older women escaped progression after 10 years. Frailty and osteoporosis were associated.

Degenerative changes of the lumbar spine may lead to misinterpretation of bone mineral density (BMD) measurements and cause underdiagnosis of osteoporosis. This longitudinal study of 1,044 women, 75 years at inclusion and followed for 10 years, shows that identification of apparent degenerative changes on the dual energy X-ray absorptiometry (DXA) scan can increase the proportion diagnosed. INTRODUCTION: In the elderly, degenerative manifestations in the lumbar spine may result in falsely elevated BMD values, consequently missing a large proportion of those with osteoporosis. Our aim was to determine the distribution and impact of degenerative changes on lumbar spine DXA over time and its clinical implications. METHODS: Participants were 1,044 women from the population-based Osteoporosis Risk Assessment cohort. All women were 75 years old at invitation and followed up after 5 years (n = 715) and 10 years (n = 382). Degenerative changes were evaluated visually on the DXA image for each vertebra L1 to L4 (intraobserver precision kappa values of 0.66-0.70). RESULTS: At baseline, apparent degenerative changes were more frequent in the inferior segments of the lumbar spine [5 % (L1), 15 % (L2), 26 % (L3), and 36 % (L4)] and increased over time. At 10 years, the prevalences were 20 % (L1), 39 % (L2), 59 % (L3), 72 % (L4), resulting in a significant increase in overall BMD. In women without apparent degenerative changes, BMD remained stable between 75 and 85 rather than an expected bone loss. At baseline, 37 % had osteoporosis (BMD < -2.5) at L1-L4; exclusion of women with apparent degenerative changes increased this proportion to 47 %. Using L1-L2, which was less prone to degenerative changes, 46 % of women were classified as osteoporotic regardless of degenerative changes. CONCLUSION: Degenerative changes were very common in elderly women, accelerated disproportionately over time, were increasingly frequent from vertebrae L1 to L4, and had significant impact on diagnosing osteoporosis. This suggests that routine reporting of spine BMD at L1-L2 would add valuable information for reassessment and monitoring.

Recreational physical activity in 25-year-old women in Sweden increases bone mineral density (BMD) in the trochanter by 5.5% when combining regularity and impact. Jogging and spinning were especially beneficial for hip BMD (6.4-8.5%). Women who enjoyed physical education in school maintained their higher activity level at age 25. INTRODUCTION: The aims of this study were to evaluate the effects of recreational exercise on BMD and describe how exercise patterns change with time in a normal population of young adult women. METHODS: In a population-based study of 1,061 women, age 25 (±0.2), BMD was measured at total body (TB-BMD), femoral neck (FN-BMD), trochanter (TR-BMD), and spine (LS-BMD). Self-reported physical activity status was assessed by questionnaire. Regularity of exercise was expressed as recreational activity level (RAL) and impact load as peak strain score (PSS). A permutation (COMB-RP) was used to evaluate combined endurance and impacts on bone mass. RESULTS: More than half of the women reported exercising on a regular basis and the most common activities were running, strength training, aerobics, and spinning. Seventy percent participated in at least one activity during the year. Women with high RAL or PSS had higher BMD in the hip (2.6-3.5%) and spine (1.5-2.1%), with the greatest differences resulting from PSS (p < 0.001-0.02). Combined regularity and impact (high-COMB-RP) conferred the greatest gains in BMD (FN 4.7%, TR 5.5%, LS 3.1%; p < 0.001) despite concomitant lower body weight. Jogging and spinning were particularly beneficial for hip BMD (+6.4-8.5%). Women with high-COMB-RP scores enjoyed physical education in school more and maintained higher activity levels throughout compared to those with low scores. CONCLUSION: Self-reported recreational levels of physical activity positively influence BMD in young adult women but to maximize BMD gains, regular, high-impact exercise is required. Enjoyment of exercise contributes to regularity of exercising which has short- and long-term implications for bone health.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mineral density and increased fracture risk. Although the genetic basis of osteoporosis is incompletely understood, previous studies have identified a polymorphism affecting an Sp1 binding site in the COLIA1 gene that predicts bone mineral density and osteoporotic fractures in several populations. Here we investigated the role of COLIA1 genotyping and bone densitometry in the prediction of osteoporotic fractures in a prospective, population-based study of men (n = 156) and women (n = 185) who were followed up for a mean (+/- SEM) of 4.88+/-0.03 years. There was no significant difference in bone density, rate of bone loss, body weight, height, or years since menopause between the genotype groups but women with the 'ss' genotype were significantly older than the other genotype groups (p = 0.03). Thirty-nine individuals sustained 54 fractures during follow-up and these predominantly occurred in women (45 fractures in 30 individuals). Fractures were significantly more common in females who carried the COLIA1 's' allele (p = 0.001), although there was no significant association between COLIA1 genotype and the occurrence of fractures in men. Logistic regression analysis showed that carriage of the COLIA1 's' allele was an independent predictor of fracture in women with an odds ratio (OR) [95% CI] of 2.59 [1.23-5.45], along with spine bone mineral density (OR = 1.57 [1.04-2.37] per Z-score unit) and body weight (OR = 1.05 [1.01-1.10] per kilogram). Moreover, bone densitometry and COLIA1 genotyping interacted significantly to enhance fracture prediction in women (p = 0.01), such that the incidence of fractures was 45 times higher in those with low BMD who carried the 's' allele (24.3 fractures/100 patient-years) compared with those with high BMD who were 'SS' homozygotes (0.54 fracture/100 patient-years). We conclude that in our population, COLIA1 genotyping predicts fractures independently of bone mass and interacts with bone densitometry to help identify women who are at high and low risk of sustaining osteoporotic fractures.

Previous studies have identified an association between osteoporotic fracture and a polymorphism affecting a Sp1 binding site in the first intron of the collagen type I alpha 1 gene (COL1A1). It is currently unclear, however, whether this association is direct or the result of linkage disequilibrium with other polymorphisms situated nearby. In this study we analyzed the relationship between four well-characterized single-nucleotide polymorphisms at the COL1A1 locus and osteoporotic fracture in 93 patients with vertebral fracture and 88 age-matched controls randomly selected from the community. We studied a MspI polymorphism 26 kb upstream of the COLIA1 gene, the Sp1 binding site polymorphism in intron 1, a RsaI polymorphism in intron 5 and a MnlI polymorphism in exon 52. The Sp1 and RsaI polymorphisms were in strong linkage disequilibrium (chi 2 = 77.87, p < 0.001) and weaker linkage disequilibrium was detected between the Sp1 and MnlI polymorphisms (chi 2 = 5.54, p < 0.025). There was a significant association between COL1A1 haplotypes that included the Sp1 and RsaI polymorphisms and fracture (p < 0.05-0.001), but no association with haplotypes that included only the MspI and MnlI polymorphisms. This association with fracture was strongest when haplotypes were grouped by Sp1 alleles (chi 2 = 11.15, d.f. = 1; p = 0.001). Furthermore, logistic regression analysis showed that of all the polymorphisms tested, only the Sp1 binding site polymorphism acted as an independent predictor of fracture: odds ratio [95% CI] = 2.26 [1.09-4.69]. These data suggest that it is the Sp1 polymorphism rather than other polymorphisms at the COL1A1 locus which act as a marker for osteoporotic fractures.