Vertebral fractures are increased in rheumatoid arthritis despite recent therapeutic advances: a case-control study.

Prevalence and risk factors of vertebral fractures in postmenopausal RA women were assessed in 323 patients and compared with 660 age-matched women. Of patients, 24.15% had at least one vertebral fracture vs.16.06% of controls. Age, glucocorticoids and falls were the main fracture risks. Vertebral fractures were associated with disease severity. INTRODUCTION: There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. METHODS: We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. RESULTS: Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. CONCLUSION: The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia?

BACKGROUND: Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase-ALP-measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. RESULTS: Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9-30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9-13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. CONCLUSIONS: In subjects with persistent hypophosphatasaemia -secondary causes excluded- one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variant.