Background: The most frequent manifestation in adult hypophosphatasia (HPP) is musculoskeletal pain. The unspecific nature of its clinical presentation may prevent correct diagnosis. The aim of the study was to assess the prevalence of ALPL mutations in adult patients treated in rheumatological outpatient facilities with evident musculoskeletal symptoms typical for HPP. Methods: Over a period of 10 years 9,522 patients were screened in the rheumatology outpatient clinic of the Hanusch hospital Vienna. Serum ALP levels ≤ 40 U/L were found in 524 patients. After screening for secondary causes, 73 patients were invited for clinical evaluation. Genetic testing was performed in 23 patients with suspected HPP. Logistic regression models with Firth penalisation were used to estimate the unadjusted and BMI-adjusted association of each clinical factor with HPP. Results: Mutations in the ALPL gene were observed in 57% of genetically screened patients. Arthralgia, fractures, and pain were the leading symptoms in individuals with ALPL mutation. Chondrocalcinosis (OR 29.12; 95% CI 2.02–1593.52) and dental disease (OR 8.33; 95% CI 0.93–143.40) were associated with ALPL mutation, independent of BMI. Onset of symptoms in patients with ALPL mutation was at 35.1 (14.3) years, with a mean duration from symptoms to diagnosis of 14.4 (8.1) years. Bone mineral density (BMD) and trabecular bone score (TBS) as well as bone turnover markers were not indicative for HPP or ALPL mutation. Conclusion: HPP can mimic rheumatologic diseases. Thus, HPP should be considered as a possible diagnosis in adult patients presenting with musculoskeletal pain of unknown origin in rheumatology outpatient clinics. In patients with persistently low ALP serum levels and unclear musculoskeletal pain, HPP as the underlying cause has to be considered.

Osteocytes are terminally differentiated osteoblasts embedded within the bone matrix and key orchestrators of bone metabolism. However, they are generally not characterized by conventional bone histomorphometry because of their location and the limited resolution of light microscopy. OI is characterized by disturbed bone homeostasis, matrix abnormalities and elevated bone matrix mineralization density. To gain further insights into osteocyte characteristics and bone metabolism in OI, we evaluated 2D osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging in transiliac bone biopsy samples from children with OI type I (n = 19) and age-matched controls (n = 24). The OLS characteristics were related to previously obtained, re-visited histomorphometric parameters. Moreover, we present pediatric bone mineralization density distribution reference data in OI type I (n = 19) and controls (n = 50) obtained with a field emission scanning electron microscope. Compared to controls, OI has highly increased OLS density in cortical and trabecular bone (+50.66%, +61.73%; both p < 0.001), whereas OLS area is slightly decreased in trabecular bone (−10.28%; p = 0.015). Correlation analyses show a low to moderate, positive association of OLS density with surface-based bone formation parameters and negative association with indices of osteoblast function. In conclusion, hyperosteocytosis of the hypermineralized OI bone matrix associates with abnormal bone cell metabolism and might further impact the mechanical competence of the bone tissue.

(1) Background: Pelvic fractures (PFs) are related to osteoporosis, and represent a serious individual and socioeconomic burden. (2) Methods: We examined age- and sex-standardised incidence rates (SIRs) of PF, along with rates of all-cause overall and one-year mortality among patients with PF. We compared the mortality rates between PF patients and a matched fracture-free cohort. Patients ≥50 years old in Austria hospitalised with PF in 2010–2018, along with their dates of death, were recorded. (3) Results: We identified 54,975 patients with PF, of whom 70.9% were women. Between 2010 and 2018 the SIR of PF increased in men by 10.0%—from 125.3 (95% Confidence Interval 118.9–132.0) to 137.8 (95% CI 131.8–144.0) per 100,000—and in women by 2.7%—from 218.7 (95% CI 212.0–225.6) to 224.7 (95% CI 218.3–231.3) per 100,000. The one-year post-PF mortality rate was higher in men than in women (13.0% and 11.1%, respectively; p < 0.001). Pelvic fracture patients aged ≥65 had an elevated mortality risk (Hazard Ratio 1.75, 95% CI 1.71–1.79, p < 0.001) compared to controls. (4) Conclusions: There is a clear increase in the incidence of PF in the elderly population, with a greater increase in men over time. Pelvic fracture itself contributes to increased mortality in individuals aged 65 and above.

Objective: Patients with diabetes have an increased risk of osteoporosis and shorter life expectancy. Hip fracture (HF) is the most serious consequence of osteoporosis and is associated with increased mortality risk. We aimed to assess the association of antidiabetic medications with HF and the post-hip fracture mortality risk among diabetic patients ≥50 years. Design: In this nationwide case-control study 53 992 HF cases and 112 144 age-, sex- and region-matched non-hip fracture controls were analyzed. A cohort of hip-fractured diabetic patients were followed-up for an all-cause mortality. Methods: We defined three groups of diabetic patients based on a prescription of antidiabetic medications: group 1 treated with insulin monotherapy (G1DM), group 2 (G2DM) treated with blood glucose-lowering drugs (BGLD) only, group 3 on a combined BGLD and insulin therapy (G3DM). We applied logistic regression and Cox regression. Results: We identified 2757 G1DM patients, 15 310 G2DM patients, 3775 G3DM patients and 144 294 patients without any antidiabetic treatment. All three groups of diabetic patients had increased odds of HF compared to controls. G1DM patients aged 50–64 years (aOR: 4.80, 95% CI: 3.22–7.17) and G3DM patients (aOR: 1.39, 95% CI: 1.02–1.88) showed the highest HF odds, whereas G2DM patients had 18% decrease in HF odds than their non-diabetic controls (aOR: 0.82, 95% CI: 0.69–0.99). All diabetic patients had increased post-hip fracture mortality risk compared to non-diabetic controls. The highest mortality hazard was observed in G1DM patients, being greater for women than men (HR: 1.71, 95% CI: 1.55–1.89 and HR: 1.44, 95% CI: 1.27–1.64, respectively). Conclusions: Antidiabetic medications increase the probability of HF. Diabetic patients, who sustained HF have a higher mortality risk than non-diabetic patients.

Background and Aims: With rising rates of inflammatory bowel diseases [IBD] in older adults, management of comorbidities such as osteoporosis is becoming increasingly important. Hip fracture [HF] is the most serious consequence of low bone mineral quality and is associated with excess risk of mortality. For older IBD patients, there are only limited data available. Therefore, we aimed to assess the association of IBD with HF, and all-cause mortality risk after HF, among IBD patients older than 50 years. Methods: In a national database-registered case-control study, 56 821 HF cases aged ≥50 years, and 113 718 age-, sex- and region-matched non-hip-fracture controls, were analysed between 2012 and 2016. A history of IBD was assessed from data from Austrian social health insurance funds. Logistic regression and Cox proportional multivariate models were used to test the association of IBD with HF and post-hip fracture mortality risk. Results: A total of 531 patients were identified with IBD (25.0% men, mean age 81.2 years, standard deviation [SD] 9.7). Analysis, adjusted for anti-osteoporotic treatment, use of glucocorticoids, and selected medications, showed that IBD patients had an increased odds of HF (odds ratio [[OR] 2.22, 95% confidence interval [CI] 1.86–2.64). Patients with Crohn’s disease [CD] revealed a higher HF odds in contrast to patients with ulcerative colitis [OR 2.91, 95% CI 2.17–3.89 and OR 1.89, 95% CI 1.52–2.35, respectively]. Overall mortality risk after HF was higher among female CD patients [HR 1.75, 95% CI 1.28–2.41] than in the general population. Conclusions: IBD was strongly associated with HF in older patients. Post-hip fracture mortality risk was elevated particularly in women with CD.