Incremento della densità minerale ossea con un secondo ciclo di dodici mesi di romosozumab dopo placebo o denosumab

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Burosumab nel trattamento della osteomalacia indotta da neoplasia

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Misurare la resistenza scheletrica oltre la DEXA

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Retinal micro-vascular and aortic macro-vascular changes in postmenopausal women with primary hyperparathyroidism

Aim of the study was to evaluate the micro and macro-vascular changes in patients with primary hyperparathyroidism (PHPT) compared to controls. 30 postmenopausal PHPT women (15 hypertensive and 15 normotensive) and 30 normotensive controls underwent biochemical evaluation of mineral metabolism and measurements of arterial stiffness by 24 hour ambulatory blood pressure monitoring. Retinal microcirculation was imaged by a Retinal Vessel Analyzer. PHPT patients also underwent bone mineral density measurements and kidney ultrasound. PHPT patients had higher mean calcium and parathyroid hormone values compared to controls. Evaluating macro-vascular compartment, we found higher values of 24 hours-systolic, diastolic blood pressure, aortic pulse wave velocity (aPWV) and aortic augmentation index (Aix) in hypertensive PHPT, but not in normotensive PHPT compared to controls. The eye examination showed narrowing arterial and venular diameters of retinal vessels in both hypertensive and normotensive PHPT compared to controls. In hypertensive PHPT, 24 hours systolic blood pressure was associated only with parathyroid hormone (PTH) levels (beta = 0.36, p = 0.04). aPWV was associated with retinal diameter (beta = −0.69, p = 0.003), but not with PTH. Retinal artery diameter was associated with PTH (beta = −0.6, p = 0.008). In the normotensive PHPT, only PTH was associated with retinal artery diameter (beta = −0.60, p = 0.01) and aortic AIx (beta = 0.65, p = 0.02). In conclusion, we found macro-vascular impairment in PHPT and that micro-vascular impairment is negatively associated with PTH, regardless of hypertension in PHPT

Naso-Ethmoidal Phosphaturic Mesenchymal Tumor: A Rare Tumor Site for an Uncommon Paraneoplastic Syndrome

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Osteomalacia and Vitamin D Status: A Clinical Update 2020

Historically, rickets and osteomalacia have been synonymous with vitamin D deficiency dating back to the 17th century. The term osteomalacia, which literally means soft bone, was traditionally applied to characteristic radiologically or histologically documented skeletal disease and not just to clinical or biochemical abnormalities. Osteomalacia results from impaired mineralization of bone that can manifest in several types, which differ from one another by the relationships of osteoid (ie, unmineralized bone matrix) thickness both with osteoid surface and mineral apposition rate. Osteomalacia related to vitamin D deficiency evolves in three stages. The initial stage is characterized by normal serum levels of calcium and phosphate and elevated alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)2D]—the latter a consequence of increased PTH. In the second stage, serum calcium and often phosphate levels usually decline, and both serum PTH and alkaline phosphatase values increase further. However, serum 1,25(OH)2D returns to normal or low values depending on the concentration of its substrate, 25-hydroxyvitamin D (25OHD; the best available index of vitamin D nutrition) and the degree of PTH elevation. In the final stage, hypocalcemia and hypophosphatemia are invariably low with further exacerbation of secondary hyperparathyroidism. The exact,or even an approximate, prevalence of osteomalacia caused by vitamin D deficiency is difficult to estimate, most likely it is underrecognized or misdiagnosed as osteoporosis. Signs and symptoms include diffuse bone, muscle weakness, and characteristic fracture pattern, often referred to as pseudofractures, involving ribs, scapulae, pubic rami, proximal femurs, and codfish-type vertebrae. The goal of therapy of vitamin D-deficiency osteomalacia is to alleviate symptoms, promote fracture healing, restore bone strength, and improve quality of life while correcting biochemical abnormalities. There is a need for better understanding of the epidemiology of osteomalacia. Simplified tools validated by concurrent bone histology should be developed to help clinicians promptly diagnose osteomalacia

"Non-phosphaturic" variant of phosphaturic mesenchymal tumor of the middle ear expressing multiple phosphatonins

Phosphaturic mesenchymal tumors (PMTs) are rare tumors commonly arising in soft tissues and bones. They are the main cause of tumor-induced osteomalacia (TIO), a paraneoplastic syndrome caused by production of FGF23 and other phosphatonins. “Non-phosphaturic” variant of PMTs (i.e., not associated with TIO) have been also reported. We describe a patient with a PMT of the middle ear, a very rare site for PMTs, in which TIO failed to develop although three phosphatonins were expressed

Age-specific effects of estrogen receptors' polymorphisms on the bone traits in healthy fertile women: the BONTURNO study

<p>Abstract</p> <p>Background</p> <p>Skeletal characteristics such as height (Ht), bone mineral density (BMD) or bone turnover markers are strongly inherited. Common variants in the genes encoding for estrogen receptor alpha (ESR1) and beta (ESR2) are proposed as candidates for influencing bone phenotypes at the population level.</p> <p>Methods</p> <p>We studied 641 healthy premenopausal women aged 20–50 years (yrs) participating into the BONTURNO study. Exclusion criteria were irregular cyclic menses, low trauma fracture, metabolic bone or chronic diseases. Serum C-telopeptide of type I collagen (CTX), osteocalcin (OC), and N-terminal propeptide of type I procollagen (P1NP) were measured in all enrolled subjects, who underwent to lumbar spine (LS), total hip (TH) and femoral neck (FN) BMD evaluation by DXA. Five hundred seventy Caucasian women were genotyped for ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms.</p> <p>Results</p> <p>Although no genotype differences were found in body parameters, subjects with combined ESR1 CCGG plus ESR2 AA-AG genotype were taller than those with opposite genotype (P = 0.044). Moreover, ESR1 rs2234693 genotypes correlated with family history of osteoporosis (FHO) and hip fracture (FHF) (P < 0.01), while ESR2 AA-AC genotypes were strongly associated with FHF (OR 2.387, 95% CI 1.432–3.977; P < 0.001).</p> <p>When clustered by age, 20–30 yrs old subjects, having at least one ESR1 rs2234693 C allele presented lower LS- (P = 0.008) and TH-BMD (P = 0.047) than TT genotypes. In 41–50 yrs age, lower FN-BMD was associated with ESR2 AA (P = 0.0180) subjects than in those with the opposite genotype. ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms did not correlate with age-adjusted values of OC, CTX and P1NP.</p> <p>Conclusion</p> <p>These findings support the presence of age-specific effects of ESR1 and ESR2 polymorphisms on various skeletal traits in healthy fertile women.</p

Tumor-Induced Osteomalacia : A Systematic Clinical Review of 895 Cases

Tumor-induced osteomalacia (TIO) is a rare and largely underdiagnosed paraneoplastic condition. Previous reviews often reported incomplete data on clinical aspects, diagnosis or prognosis. The aim of this study was to present a systematic clinical review of all published cases of TIO. A search was conducted in Pubmed, Embase, Web of Science from inception until April 23rd, 2020. We selected case reports and case series of patients diagnosed with TIO, with information on tumor localization and serum phosphate concentration. Two reviewers independently extracted data on biochemical and clinical characteristics including bone involvement, tumor localization and treatment. 468 articles with 895 unique TIO cases were included. Median age was 46 years (range 9 months–90 years) and 58.3% were males. Hypophosphatemia and inappropriately low or normal 1,25-dihydroxyvitamin D levels, characteristic for TIO, were present in 98% of cases. Median tumor size was 2.7 cm (range 0.5 to 25.0 cm). Serum fibroblast growth factor 23 was related to tumor size (r = 0.344, P < 0.001). In 32% of the cases the tumor was detected by physical examination. Data on bone phenotype confirmed skeletal involvement: 62% of cases with BMD data had a T-score of the lumbar spine ≤ − 2.5 (n = 61/99) and a fracture was reported in at least 39% of all cases (n = 346/895). Diagnostic delay was longer than 2 years in more than 80% of cases. 10% were reported to be malignant at histology. In conclusion, TIO is a debilitating disease characterized by a long diagnostic delay leading to metabolic disturbances and skeletal impairment. Increasing awareness of TIO should decrease its diagnostic delay and the clinical consequences

Vitamin D and Its Relationship with Obesity and Muscle

The skin synthesis of vitamin D represents the first step of a metabolic pathway whose features have been extensively studied and clarified in the last decades. In particular, the production of active and inactive forms of the hormone and the actions of the corresponding enzymes have offered new insights into the knowledge of vitamin D metabolism. Additionally, the description of the different organs and tissues expressing the vitamin D receptor and its possible functions, as well as its genetic determinants, have allowed focusing on the interrelationship between vitamin D and many physiological and pathological functions. In this context, many studies reported the association between vitamin D and adipose tissue metabolism, as well as the possible role of the hormone in obesity, weight, and fat mass distribution. Finally, many reports focused on the vitamin D-related effects on skeletal muscle, particularly on the mechanisms by which vitamin D could directly affect muscle mass and strength. This paper is mainly aimed to review vitamin D metabolism and its relationship with obesity and skeletal muscle function