Multidimensional prognostic index and the risk of fractures: an 8-year longitudinal cohort study in the Osteoarthritis Initiative

Summary In this longitudinal study, with a follow-up of 8 years, multidimensional prognostic index (MPI), a product of the comprehensive geriatric assessment, significantly predicted the onset of fractures in older people affected by knee osteoarthritis. Purpose Frailty may be associated with higher fracture risk, but limited research has been carried out using a multidimensional approach to frailty assessment and diagnosis. The present research aimed to investigate whether the MPI, based on comprehensive geriatric assessment (CGA), is associated with the risk of fractures in the Osteoarthritis Initiative (OAI) study. Methods Community-dwellers affected by knee OA or at high risk for this condition were followed-up for 8 years. A standardized CGA including information on functional, nutritional, mood, comorbidity, medication, quality of life, and co-habitation status was used to calculate the MPI. Fractures were diagnosed using self-reported information. Cox’s regression analysis was carried out and results are reported as hazard ratios (HRs), with their 95% confidence intervals (CIs), adjusted for potential confounders. Results The sample consisted of 4024 individuals (mean age 61.0 years, females = 59.0%). People with incident fractures had a significant higher MPI baseline value than those without (0.42 ± 0.18 vs. 0.40 ± 0.17). After adjusting for several potential confounders, people with an MPI over 0.66 (HR = 1.49; 95%CI: 1.11–2.00) experienced a higher risk of fractures. An increase in 0.10 point in MPI score corresponded to an increase in fracture risk of 4% (HR = 1.04; 95%CI: 1.008–1.07). Higher MPI values were also associated with a higher risk of non-vertebral clinical fractures. Conclusion Higher MPI values at baseline were associated with an increased risk of fractures, reinforcing the importance of CGA in predicting fractures in older people affected by knee OA.

Objectively Measured Physical Activity, Sedentary Behavior, and Incident Fracture in Older Women: The OPACH Study

Women aged 65 and older experience nearly three-fourths of the 2 million osteoporotic fractures annually in the US, yet whether accelerometer-measured volumes and intensities of physical activity and sedentary behavior (SB) are associated with reduced fracture risk is understudied. We investigated associations of accelerometer-measured light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time (ST), and mean sedentary bout duration (MBD) with incident clinical fractures (hip, vertebral, pelvis, lower leg, upper arm, forearm, and wrist) in the WHI OPACH cohort. Participants (N=6248; mean±SD age=78.6±6.7; 34% Black, 17% Hispanic) without prior hip fracture wore the ActiGraph GT3X+ for 7 days between May 2012-April 2014 and were followed through March 2020 for incident clinical fracture (N=711). Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI), adjusting for age, race-ethnicity, education, alcohol, smoking, height, weight, falls history, RAND-36 physical function, diabetes, thiazide use, prescription osteoporotic therapy, and age at menopause. The HR(95% CI) across MVPA quartiles was 1.00(reference), 1.15(0.93-1.41), 0.90(0.72-1.13), and 0.79(0.61-1.02); p-trend=0.01. The HR(95% CI) for a one-interquartile range increment in MVPA (42 minutes/day) was 0.86(0.76-0.97). Associations were modified by prescription osteoporotic therapy [no: HR=0.77(0.66-0.89), yes: HR=1.03(0.85-1.25); p-interaction=0.01] and varied in magnitude by age[<80: HR=0.78(0.64-0.96), ≥80: HR=0.92(0.79-1.07); p-interaction=0.09], BMI [<30 kg/m2: HR=0.85(0.75-0.97), ≥30 kg/m2: HR=0.90(0.67-1.19); p-interaction=0.08], and race-ethnicity [Black: HR =0.63(0.44-0.89), Hispanic: HR =0.78(0.56-1.09), White: HR =0.92(0.80-1.06); p-interaction=0.16]. LPA, ST, or MBD were not associated with incident fractures. These data suggest that MVPA may reduce and not increase fracture risk and that LPA and SB do not increase fracture risk.

Influence of Serum Biochemistry on Bone and Kidney Phenotypes in Subjects With Symptomatic Primary Hyperparathyroidism

OBJECTIVETo analyze the abnormalities in serum parathormone (PTH)-25-hydroxy-vitamin D (25-OHD) axis and calcium phosphate homeostasis in symptomatic PHPT patients having bone disease, nephrolithiasis and impaired renal function (IRF) at diagnosis. METHODSConsecutive adults (>18 years) with diagnosed symptomatic PHPT were enrolled in the retrospective study. Relevant clinical, biochemical and imaging parameters were recorded.RESULTSAdult patients with symptomatic PHPT were identified (N=60, age 45.2±14.4 years, 45 females). Predominant phenotypes were bone disease (osteoporosis and/or clinical fractures, n=42, 70%) and nephrolithiasis (n=24, 40%). Compared to patients with nephrolithiasis only (subgroup C, n=7) and simultaneous bone disease/nephrolithiasis (subgroup D, n=17), patients with isolated bone disease phenotype (subgroup B, n=25) had significantly higher alkaline phosphatase (AlP) and lower 25-OHD levels at presentation. Patient subgroups with nephrolithiasis had higher serum calcium levels and lower effective glomerular filtration rate (eGFR) at presentation. PTH was not significantly different among these subgroups. Patients with IRF (eGFR <60 ml/min per 1.73 m2, n=17) in our cohort had significantly higher serum calcium, phosphate, PTH levels and nephrolithiasis rates. Presence of nephrolithiasis, higher calcium x phosphate product (IRF: 36.2 ± 10.7 versus no IRF: 26.2 ± 5.7 mg2/dl2) and increased PTH levels were independently associated with IRF at diagnosis.CONCLUSIONSWhile PHPT patients with isolated bone disease were found to have lower 25-OHD and higher AlP levels independent of PTH levels; PTH was found to be an independent predictor of impaired renal function at diagnosis.

The Effect of Teriparatide Treatment on the Risk of Fragility Fractures in Postmenopausal Women with Osteoporosis: Results from the Asian and Latin America Fracture Observational Study (ALAFOS)

The Asian and Latin America Fracture Observational Study (ALAFOS) is a prospective, observational, single-arm study conducted in 20 countries across Asia, Latin America and the Middle East. ALAFOS evaluated new clinical vertebral and non-vertebral fragility fractures in relation to time on teriparatide, in postmenopausal women with osteoporosis in real-life clinical practice. Clinical fragility fractures, back pain, and health-related quality of life (HRQoL) were recorded in 6-month intervals for ≤ 24 months during teriparatide treatment and up to 12-months post-treatment. Data were analysed with piecewise exponential regression with inverse probability weighting for time to event outcomes and mixed-model repeated measures for back pain and HRQoL. 3054 postmenopausal women started teriparatide and attended ≥ one follow-up visit (mean [SD] age 72.5 [10.4] years). The median (95% CI) time to treatment discontinuation was 22.0 months (21.2, 22.8). During the treatment period, 111 patients (3.6%) sustained 126 clinical fractures (2.98 fractures/100 patient-years). Rates of new clinical fragility fractures were significantly decreased during the > 6–12, > 12–18, and > 18–24-month periods, as compared with the first 6 months of treatment (hazard ratio [HR] 0.57; 95% CI 0.37, 0.88; p = 0.012; HR 0.35; 95% CI 0.19, 0.62; p < 0.001; HR 0.43; 95% CI 0.23, 0.83; p = 0.011; respectively). Patients also reported an improvement in back pain and HRQoL (p < 0.001). These results provide data on the real-world effectiveness of teriparatide in the ALAFOS regions and are consistent with other studies showing reduction of fractures after 6 months of teriparatide treatment. These results should be interpreted in the context of the noncontrolled design of this observational study.

POS0466 RHEUMATOID ARTHRITIS PER SE IS NOT RISK FACTOR FOR CLINICAL FRACTURES: NINE-YEAR FINDINGS OF THE TOMORROW STUDY

Background:Patients with rheumatoid arthritis (RA) who have sarcopenia and stiff or painful joints might be at increased risk of falls and fractures.Objectives:The present study aimed to prospectively identify the incidence of clinical fractures and associated risk factors in patients with RA in a cohort study named the TOMORROW (UMIN000003876) that started in 2010.Methods:We evaluated anthropometric parameters, bone mineral density (BMD), disease activity, RA medication at baseline and observed the incidence of clinical fractures during nine years in 202 patients with RA (mean age, 58.6 y; medication with biological agents, 54.9%) and 202 age- and sex-matched non-RA volunteers (mean age, 57.4 y). We compared the incidence of clinical fractures between patients with RA and controls for nine years, and analyzed the risk factors for fractures using Cox proportional hazard model.Results:The incidence of clinical fractures in RA patients was significantly higher compared to controls (27.5 vs 18.3%, p=0.04). However, Cox proportional hazard model, adjusted by age, sex, smoking and body mass index, revealed that low BMD at thoracic vertebrae (< 0.7 g/cm2) significantly associated to the incidence of clinical fractures (hazard ratio [HR], 1.86, p=0.02), but not RA morbidity (HR 1.47, p=0.10) (Table 1). Among patients with RA, low BMD at the thoracic vertebrae (< 0.7 g/cm2) was the most prominent risk factor for clinical fractures (HR, 2.66, p=0.02) (Table 1). Although the use of glucocorticoid (GC) at baseline (HR, 1.68, p=0.09) was not a significant risk factor for fractures, a mean GC dose (≥ 2 mg/day) at entry increased risk for clinical fractures in the patients (HR, 1.91, p=0.04) (Table 1).Conclusion:RA per se was not a risk factor for clinical fractures in this cohort. Low BMD at the thoracic vertebrae and the use of GC with even low dose at entry were apparently significant risk factors for the incidence of clinical fractures among patients with RA.Disclosure of Interests:Kenji Mamoto: None declared, Tatsuya Koike Grant/research support from: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation,Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, Yutaro Yamada: None declared, Tadashi Okano: None declared, Yuko Sugioka: None declared, Masahiro Tada: None declared, Kentaro Inui Speakers bureau: Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Takeda Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Abbvie GK, Pfizer Inc., Eisai Co.,Ltd., Chugai Pharmaceutical Co., Ltd., Grant/research support from: Janssen Pharmaceutical K.K., Astellas Pharma Inc., Sanofi K.K., Abbvie GK, Takeda Pharmaceutical Co. Ltd., QOL RD Co. Ltd., Mitsubishi Tanabe Pharma, Ono Pharmaceutical Co. Ltd., Eisai Co.,Ltd., Hiroaki Nakamura: None declared

POS0171 UNDERESTIMATION OF THE FRACTURE RISK BY THE FRAX FORMULA IN CHRONIC GLUCOCORTICOID USERS: A 10-YEAR LONGITUDINAL VALIDATION STUDY

Background:Objectives:To compare the actual fracture incidence over 10 years in a longitudinal cohort of patients using glucocorticoids (GCs) with the risk prediction from FRAX (fracture risk assessment tool).Methods:Patients who attended our out-patient rheumatology clinics were included according to the following criteria: (1) adult patients ≥18 years; (2) underlying rheumatic diseases requiring prednisolone treatment (≥5mg/day); and (3) have had a DXA scan (baseline) performed between years 2007-2009. The predicted rates of major osteoporotic and hip fractures were estimated using FRAX (China database) based on the clinical data at the time of DXA, with adjustment when daily dose of prednisolone ≥7.5mg (multiply by 1.15 for major osteoporotic and 1.20 for hip fracture). The actual observed incidence of symptomatic vertebral and non-vertebral fractures at 10 years (in years 2017-2019) follow-up was retrieved by medical record review and compared with the estimated rates by FRAX. Factors associated with symptomatic clinical fractures at 10 years were studied by logistic regression.Results:89 patients were studied (age 49.3±8.8 years at DXA examination; 98% women). The underlying rheumatic diseases were systemic lupus erythematosus (69%), rheumatoid arthritis (17%) and others (14%). The mean daily dose of prednisolone at baseline was 7.7±6.5mg (38% patients had daily dose ≥7.5mg). History of personal fracture was present in 4(4.5%) patients and 22% of female patients had menopause before the age of 45 years. The mean body mass index (BMI) was 23.5±3.3kg/m2 (4.5% ≤18kg/m2). Osteoporosis (bone mineral density [BMD] T score ≤-2.5) of the hip, femoral neck and lumbar spine occurred at a frequency of 11.2%, 13.5% and 25.8%, respectively at baseline (32% at any of the 3 sites). 30(34%) patients received anti-osteoporotic treatment (oral bisphosphonates in 25, raloxifene in 3 and denosumab in 2 patients). The estimated mean 10-year risk of major osteoporotic and hip fractures using the BMD data and other risk factors in the FRAX formula, adjusted for prednisolone dose, was 4.3% and 1.0%, respectively. After a follow-up of 10 years, one patient had a hip fracture, 3 patients had humerus fractures and 9 patients had symptomatic vertebral fractures. The actual observed major osteoporotic and hip fracture incidence was 14.6% and 1.1%, respectively (0.146 and 0.011 per 10 patient-years). The observed major clinical fracture rate was significantly higher than that estimated by FRAX (14.6% vs 4.3%; p=0.04). Logistic regression revealed that the only factor independently associated with major clinical fracture at 10 years was BMD T score ≤-2.5 at spine, hip or femoral neck at baseline (OR7.11[1.73-29.2]; p=0.007). Age, prednisolone daily dose, BMI, history of fracture, chronic smoking, having underlying SLE vs not and early menopause were not significantly associated with new clinical fractures.Conclusion:Despite adjustment for prednisolone dosage, the FRAX formula underestimates the major clinical fracture risk in patients using long-term GCs. The deleterious effect of GCs on bone quality, high proportion of SLE patients, disease activity and use of additional doses of GCs and other immunosuppressive drugs during follow-up are among the contributing factors for this underestimation.Disclosure of Interests:None declared

OP0323 INCIDENCE OF CLINICAL FRAGILITY FRACTURES IN POSTMENOPAUSAL WOMEN WITH RHEUMATOID ARTHRITIS. A MULTICENTRIC CASE-CONTROL STUDY

Background:Incidence of clinical fractures in rheumatoid arthritis (RA) is not as well-known as hip or vertebral fracture incidence.Objectives:1. To estimate the incidence of clinical fragility fractures in a population of postmenopausal women diagnosed with RA and compare it with that of the general population; 2. To analyze the risk factors for fracture.Methods:330 postmenopausal women with RA from 19 Spanish Rheumatology Departments, randomly selected from the registry of RA patients in each center. The control group consisted of 660 Spanish postmenopausal women from the Camargo Cohort. Clinical fractures during the previous 5 years were recorded. Assessed risk factors for fracture were: sociodemographic characteristics, BMD and variables related to RA.Results:Median age of RA patients was 64 yrs. vs. 63 yrs. in controls (ns). Evolution of the disease was 8 yrs. 78% and 76% had RF and ACPA+, respectively. 69% of patients were in remission or low activity. 85% had received glucocorticoids and methotrexate and 40% at least one biological DMARD. We identified 105 fractures (87 fragility and 18 traumatic) in 75 patients. Fifty-four patients and 47 controls had at least one major fracture (MF) (p< 0.001). Incidence of MF was 3.55 per 100 patient-year in patients and 0.72 in controls. Risk factors for MF in RA patients were age, previous fracture, parental hip fracture, postmenopausal period, hip BMD and cumulative dose of glucocorticoids. In controls, risk factors were age, age at menopause and lumbar BMD.Among RA-associated factors, MFs were associated with erosions, disease activity and disability. Previous fracture in RA patients was a strong risk for MF (HR: 10.37 [95% CI: 2.95-36.41]).Conclusion:Between 3 and 4 of every 100 postmenopausal women with RA have a major fracture per year, four times more than the general population. Disease activity and disability associated with RA, the cumulative dose of glucocorticoids and mainly previous fracture are associated with the development of fragility fractures.References:NoneAcknowledgments:Funded in part by ISCIII (PI18/00762) that included FEDER funds from the EU.Disclosure of Interests:Carmen Gómez Vaquero: None declared, Jose Manuel Olmos: None declared, J. Luis Hernández: None declared, Dacia Cerda: None declared, Cristina Hidalgo: None declared, JA Martínez López: None declared, Luis Marcelino Arboleya Rodríguez: None declared, Javier Aguilar del Rey: None declared, Silvia Martinez Pardo: None declared, Inmaculada Ros: None declared, Xavier Surís: None declared, Dolors Grados Canovas: None declared, Chesús Beltrán Audera: None declared, Evelyn Suero-Rosario: None declared, Inmaculada Gómez Gracia: None declared, Asunción Salmoral: None declared, Irene Martín-Esteve: None declared, Helena Florez: None declared, Antonio Naranjo Grant/research support from: amgen, Consultant of: UCB, Speakers bureau: AMGEN, Santos Castañeda: None declared, Soledad Ojeda Speakers bureau: AMGEN, LILLY, GEBRO, S García Carazo: None declared, Alberto García-Vadillo: None declared, Laura López Vives: None declared, À Martínez-Ferrer: None declared, Helena Borrell Paños: None declared, Pilar Aguado: None declared, Raul Castellanos-Moreira: None declared, Cristian Tebé: None declared, Núria Guañabens: None declared