Analysis of circulating osteoclast and osteogenic precursors in patients with Gorham-Stout disease.

PURPOSE: Gorham-Stout disease is a very rare disorder characterized by progressive bone erosion and angiomatous proliferation; its etiopathogenesis is still unknown, and diagnosis is still performed by exclusion criteria. The alteration of bone remodeling activity has been reported in patients; in this study, we characterized circulating osteoclast and osteogenic precursors that could be important to better understand the osteolysis observed in patients. METHODS: Flow cytometry analysis of PBMC (Peripheral Blood Mononuclear Cells) was performed to characterize circulating osteoclast and osteogenic precursors in GSD patients (n = 9) compared to healthy donors (n = 55). Moreover, ELISA assays were assessed to evaluate serum levels of bone markers including RANK-L (Receptor activator of NF-κB ligand), OPG (Osteoprotegerin), BALP (Bone Alkaline Phosphatase) and OCN (Osteocalcin). RESULTS: We found an increase of CD16-/CD14+CD11b+ and CD115+/CD14+CD11b+ osteoclast precursors in GSD patients, with high levels of serum RANK-L that could reflect the increase of bone resorption activity observed in patients. Moreover, no significant alterations were found regarding osteogenic precursors and serum levels of BALP and OCN. CONCLUSION: The analysis of circulating bone cell precursors, as well as of RANK-L, could be relevant as an additional diagnostic tool for these patients and could be exploited for therapeutic purposes.

Bone loss after discontinuation of denosumab: the devil is in the details.

A 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications.

Nutrition, Vitamin D, and Calcium in Elderly Patients before and after a Hip Fracture and Their Impact on the Musculoskeletal System: A Narrative Review.

Hip fractures are a major health issue considerably impacting patients' quality of life and well-being. This is particularly evident in elderly subjects, in which the decline in bone and muscle mass coexists and predisposes individuals to fall and fracture. Among interventions to be implemented in hip fractured patients, the assessment and management of nutritional status is pivotal, particularly in subjects older than 65. Nutrition plays a central role in both primary and secondary preventions of fracture. An adequate protein intake improves muscle mass and strength and the intestinal absorption of calcium. Other nutrients with recognized beneficial effects on bone health are calcium, vitamins D, K, and C, potassium, magnesium, folate, and carotenoids. With reference to calcium, results from longitudinal studies showed that the consumption of dairy foods has a protective role against fractures. Moreover, the most recent systematic reviews and meta-analyses and one umbrella review demonstrated that the combination of calcium and vitamin D supplementation significantly reduces hip fracture risk, with presumed higher efficacy in older and institutionalized subjects. Owing to these reasons, the adequate intake of calcium, vitamin D, protein, and other macro and micronutrients has been successfully implemented in the Fracture Liaison Services (FLSs) that represent the most reliable model of management for hip fracture patients. In this narrative review, papers (randomized controlled trials, prospective and intervention studies, and systematic reviews) retrieved by records from three different databases (PubMed, Embase, and Medline) have been analyzed, and the available information on the screening, assessment, and management of nutritional and vitamin D status and calcium intake in patients with hip fractures is presented along with specific prevention and treatment measures.

Effect of 2 Years of Monthly Calcifediol Administration in Postmenopausal Women with Vitamin D Insufficiency.

BACKGROUND: We assessed the long-term (24 months) efficacy and safety of monthly calcifediol (0.266 mg) in the correction and maintenance of total 25(OH)D levels in postmenopausal women with basal values <30 ng/mL. METHODS: We initially enrolled 45 consecutive patients during the period September 2019-September 2020. After an initial visit, patients were instructed to return at 3, 6, 9, 12 and 24 months for measuring serum total 25(OH)D, ionised calcium, creatinine and isoenzyme of alkaline phosphatase (bALP). Here, we report only the per-protocol analysis, because the COVID-19 pandemic precluded adherence to the scheduled visits for some patients. RESULTS: The patients' mean age was 62.4 ± 9.0 years. Mean basal 25(OH)D levels were 20.5 ± 5.3 ng/mL. There was a continuous increase of mean 25(OH)D values (p for trend < 0.001). However, mean values at month 24 (36.7 ± 15.9) were not significantly different in respect to values at month 12 (41.2 ± 11.18). At 24 months, only 1 out 19 patients had a value <20 ng/mL. There was a significant decrease with time of mean values of bALP (p < 0.0216), with no significant changes between 12 and 24 months. No significant changes were observed as far as ionised calcium or creatinine were concerned. CONCLUSIONS: The long-term administration of calcifediol maintains stable and sustained 25(OH)D concentrations, with no safety concerns.

Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.