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IntroductionHypophosphatasia (HPP) is a rare genetic disease caused by inactivating variants of the ALPL gene. Few data are available on the clinical presentation in Italy and/or on Italian HPP surveys.MethodsThere were 30 suspected HPP patients recruited from different Italian tertiary cares. Biological samples and related clinical, biochemical, and anamnestic data were collected and the ALPL gene sequenced. Search for large genomic deletions at the ALPL locus (1p36) was done. Phylogenetic conservation and modeling were applied to infer the effect of the variants on the protein structure.ResultsThere were 21 ALPL variants and one large genomic deletion found in 20 out of 30 patients. Unexpectedly, NGS-driven differential diagnosis allowed uncovering three hidden additional HPP cases, for a total of 33 HPP subjects. Eight out of 24 coding variants were novel and classified as “pathogenic”, “likely pathogenic”, and “variants of uncertain significance”. Bioinformatic analysis confirmed that all the variants strongly destabilize the homodimer structure. There were 10 cases with low ALP and high VitB6 that resulted negative to genetic testing, whereas two positive cases have an unexpected normal ALP value. No association was evident with other biochemical/clinical parameters.DiscussionWe present the survey of HPP Italian patients with the highest ALPL mutation rate so far reported and confirm the complexity of a prompt recognition of the syndrome, mostly for HPP in adults. Low ALP and high VitB6 values are mandatory for the genetic screening, this latter remaining the gold standard not only to confirm the clinical diagnosis but also to make differential diagnosis, to identify carriers, to avoid likely dangerous therapy in unrecognized cases.

IntroductionPsychological features have been bidirectionally associated with osteoporosis, but it is still unclear whether patient’s anxiety fluctuations during the anti-osteoporotic treatment can have an impact on bone mineral density (BMD) variation. The aim of this study was to investigate the interrelations between psychological distress features, such as anxiety, depression, health-related QoL (HRQoL) and bone health in women receiving anti-osteoporotic treatment.Methods192 post-menopausal osteoporotic women were treated with alendronate or risedronate according to the standard procedure. The levels of anxiety, depression, and perceived HRQoL, along with BMD, were assessed at baseline and at a 2-year follow-up.ResultsAt the end of the study, the patients showed a statistically significant increase of both psychic and somatic anxiety (p

There is growing interest in the relationship between chronic kidney disease (CKD) and fragility fracture risk. Bone mineral density (BMD) is a major determinant of bone strength, although its role as a predictor of fracture in advanced CKD and hemodialysis is still under debate. We aimed to further investigate surrogates of bone quality and their associations with muscle strength and fracture risk in hemodialysis. Multiple clinical risk factors for fracture and an estimated 10-year probability of fracture, BMD at lumbar spine and femur, trabecular bone score (TBS), X-ray vertebral morphometry, phalangeal bone quantitative ultrasonography (QUS), tibial pulse-echo ultrasonography (PEUS), and handgrip strength were evaluated in a setting of hemodialysis patients in treatment with acetate-free biofiltration (AFB) or bicarbonate hemodialysis. The bone ultrasound measurements, both at phalangeal and tibial sites, were significantly associated with lumbar and femoral DXA values. Handgrip strength was significantly associated with the 10-year probability of fracture (r = −0.57, p < 0.001 for major fractures and r = −0.53, p < 0.001 for hip fracture, respectively), with femur neck, total femur, and L1–L4 BMD values (r = 0.47, p = 0.04; r = 0.48, p = 0.02; r = 0.58, p = 0.007, respectively), with TBS at the lumbar spine (r = 0.71, p < 0.001) and with the phalangeal QUS measure of AD-SoS (r = 0.369, p = 0.023). In the hemodialysis group, 10 participants (24.3%) reported at least one morphometric vertebral fracture (Vfx); conversely, only six participants (15%) showed Vfx in the control group. In the hemodialysis group, participants with Vfx compared with participants without Vfx reported significantly different TBS, bone transmission time (BTT), cortical thickness, and handgrip strength (p < 0.05). At multiple regression analysis, by identifying as dependent variable the 10-year fracture risk for major fracture, after correcting for age, BMI, time since dialysis, AD-SoS, cortical bone thickness, and handgrip strength, only BTT (β = −15.21, SE = 5.91, p = 0.02) and TBS (β = −54.69, SE = 21.88, p = 0.02) turned out as independently associated with fracture risk. In conclusion, hemodialysis patients showed a higher fracture risk and lower surrogate indices of bone strength as TBS and QUS parameters. In this cohort of patients, handgrip strength measurements appeared to be a useful instrument to identify high-fracture-risk subjects.