Cinacalcet increases renal calcium excretion in PTHrP-mediated hypercalcemia: a case report.

Background: In the acute setting, PTH-independent hypercalcemia is typically treated with anti-resorptive agents such as zoledronic acid or denosumab. When these agents are no longer able to control hypercalcemia, several case reports have shown the utility of cinacalcet. However, it is not known if cinacalcet can be effective in patients naïve to anti-resorptive therapy or how cinacalcet ameliorates the hypercalcemia.

Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone (1-84) in Adults With Chronic Hypoparathyroidism.

Context: Chronic hypoparathyroidism is conventionally treated with oral calcium and active vitamin D to reach and maintain targeted serum calcium and phosphorus levels, but some patients remain inadequately controlled.

Objective: To assess long-term safety and efficacy of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) treatment.

Methods: This was an open-label extension study at 12 US centers.

Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review.

The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. Enhanced attention by endocrine surgeons to new knowledge about parathyroid gland viability are reviewed along with the role of intraoperative parathyroid hormone (ioPTH) monitoring during and after neck surgery. Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key.

Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines from the Second International Workshop.

This clinical practice guideline addresses the prevention, diagnosis, and management of hypoparathyroidism (HypoPT) and provides evidence-based recommendations. The HypoPT task forces included four teams with a total of 50 international experts including representatives from the sponsoring societies. A methodologist (GG) and his team supported the taskforces and conducted the systematic reviews.

Bone marrow adipose tissue composition and glycemic improvements after gastric bypass surgery.

Fracture risk is increased in type 2 diabetes, which may in part be due to altered bone marrow adiposity. Cross sectional studies have reported that people with type 2 diabetes have lower unsaturated BMAT lipid levels than people without diabetes, although there are limited data on longitudinal changes. We hypothesized that Roux-en-Y gastric bypass (RYGB), which dramatically improves glycemic status, would have differential effects on BMAT composition, with increases in the unsaturated lipid index in people with diabetes.

Risk of Fracture Among Older Adults With Primary Hyperparathyroidism Receiving Parathyroidectomy vs Nonoperative Management.

Importance: Primary hyperparathyroidism (PHPT) contributes to the development and progression of osteoporosis in older adults. The effectiveness of parathyroidectomy for reducing fracture risk in older adults is unknown.

Objective: To compare the incidence of clinical fracture among older adults with PHPT treated with parathyroidectomy vs nonoperative management.

The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics.

Background: The PARADIGHM registry of adult and pediatric patients with chronic hypoparathyroidism evaluates the long-term safety and effectiveness of treatment with recombinant human parathyroid hormone, rhPTH(1-84), and describes the clinical disease course under conditions of routine clinical practice. In this first report, we detail the registry protocol and describe the baseline characteristics of two adult patient cohorts from an interim database analysis. One cohort after study entry were prescribed rhPTH(1-84), and the other cohort received conventional therapy of calcium and active vitamin D.

Sporadic Primary Hyperparathyroidism.

Sporadic primary hyperparathyroidism is a common endocrinopathy, particularly afflicting postmenopausal women and both African American men and women. Although classic signs and symptoms of the disease are well appreciated and described, because of the ease and availability and low threshold for screening, the disorder often is diagnosed in patients who are minimally symptomatic or asymptomatic. Surgery conducted by experienced endocrine surgeons has a high cure rate, particularly if guided by concordant imaging.

Osteoporosis and fractures in rheumatoid arthritis.

Purpose Of Review: Rheumatoid arthritis (RA) is associated with increased risk for osteoporotic fracture. We highlight RA-specific risk factors for bone mineral density (BMD) loss and fractures and considerations regarding the diagnosis and treatment of osteoporosis in patients with RA.

Recent Findings: Anticitrullinated protein antibody (ACPA) positivity, although associated with low BMD in early RA, is not associated with accelerated BMD loss over time when compared to ACPA negative individuals.

Bone age is not just for kids.

More informed discussions between physicians and older adults about the consequences of an initial osteoporotic fracture could encourage more patients to consider treatments that protect against future fracture.

PTH hypersecretion triggered by a GABA and Ca-sensing receptor heterocomplex in hyperparathyroidism.

Molecular mechanisms mediating tonic secretion of parathyroid hormone (PTH) in response to hypocalcaemia and hyperparathyroidism (HPT) are unclear. Here we demonstrate increased heterocomplex formation between the calcium-sensing receptor (CaSR) and metabotropic γ-aminobutyric acid (GABA) B receptor (GABAR) in hyperplastic parathyroid glands (PTGs) of patients with primary and secondary HPT. Targeted ablation of GABAR or glutamic acid decarboxylase 1 and 2 in PTGs produces hypocalcaemia and hypoparathyroidism, and prevents PTH hypersecretion in PTGs cultured from mouse models of hereditary HPT and dietary calcium-deficiency.

Sex differences in frailty and its association with low bone mineral density in rheumatoid arthritis.

Objectives: Frailty in the general population is associated with poor health outcomes including low bone mass and osteoporotic fracture. The relationship between frailty and low bone mineral density (BMD) in rheumatoid arthritis (RA) is unknown. This study examined associations between frailty and BMD in RA, controlling for established osteoporosis risk factors.

Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update.

Objective: The objective is to provide an update of the 2019 Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline for the pharmacological management of osteoporosis in postmenopausal women using romosozumab.

Conclusions: We reviewed findings from the meta-analysis and primary clinical trials assessing the efficacy of romosozumab, a monoclonal antibody targeting sclerostin, for the prevention of fractures and concluded that this agent can be considered a treatment option for postmenopausal women at very high risk for osteoporotic fracture. The romosozumab label has a boxed warning, recommending careful consideration by the treating clinician as to cardiovascular risk profile in the individual woman who might receive this agent, since clinical trial data from an active comparator study show an imbalance in serious cardiovascular adverse events between romosozumab and alendronate.

Increases in PYY and uncoupling of bone turnover are associated with loss of bone mass after gastric bypass surgery.

Context: The gut hormones peptide YY (PYY) and ghrelin mediate in part the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. However, preclinical data suggest these hormones also affect the skeleton and could contribute to postoperative bone loss.

Objective: We investigated whether changes in fasting serum total PYY and ghrelin were associated with bone turnover marker levels and loss of bone mineral density (BMD) after RYGB.

New Frontiers in Osteoporosis Therapy.

Current osteoporosis medications reduce fractures significantly but have rare and serious adverse effects (osteonecrosis of the jaw, atypical femoral fractures) that may limit their safety for long-term use. Insights from basic bone biology and genetic disorders have led to recent advances in therapeutics for osteoporosis. New approaches now in clinical use include the antisclerostin monoclonal antibody romosozumab, as well as the parathyroid hormone-related peptide analog abaloparatide.

Calcium-Sensing Receptors in Chondrocytes and Osteoblasts Are Required for Callus Maturation and Fracture Healing in Mice.

Calcium and its putative receptor (CaSR) control skeletal development by pacing chondrocyte differentiation and mediating osteoblast (OB) function during endochondral bone formation-an essential process recapitulated during fracture repair. Here, we delineated the role of the CaSR in mediating transition of callus chondrocytes into the OB lineage and subsequent bone formation at fracture sites and explored targeting CaSRs pharmacologically to enhance fracture repair. In chondrocytes cultured from soft calluses at a closed, unfixed fracture site, extracellular [Ca ] and the allosteric CaSR agonist (NPS-R568) promoted terminal differentiation of resident cells and the attainment of an osteoblastic phenotype.

Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism.

Context: Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency.

Objective: To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)].

Design: Open-label extension study; 5-year interim analysis.

Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline.

Objective: The objective is to formulate clinical practice guidelines for the pharmacological management of osteoporosis in postmenopausal women.

Conclusions: Evidence from clinical trials and insights from clinical experience with pharmacologic therapies for osteoporosis were critically evaluated in formulating this guideline for the management of postmenopausal osteoporosis. Patient preferences, data on adherence and persistence, and risks and benefits from the patient and provider perspectives were also considered in writing committee deliberations.