The five-year effect of a single zoledronate infusion on bone mineral density following denosumab discontinuation in women with postmenopausal osteoporosis

The long-term effects of zoledronate treatment in women with postmenopausal osteoporosis who stop denosumab therapy when they become osteopenic are not known. In a prospective, randomized, controlled clinical trial we previously reported that a single intravenous infusion of zoledronate 5 mg given to such patients 6 months after the last denosumab injection effectively prevents bone loss in the majority of them for up to 3 years. The study was extended for an additional 2 years and included all 19 patients from one Trial Site of the total 27 patients originally randomized in the zoledronate arm. Baseline characteristics of this cohort treated with denosumab for 2.4 & PLUSMN; 0.2 years were not different from those of the whole initial cohort or from the patients who did not participate in this extension. At the end of 5 years 7 patients had become again osteoporotic requiring additional treatment, 9 remained osteopenic while 3 did not complete the study extension. Thus, more than half of the osteoporotic women who became osteopenic with denosumab treatment and stopped it, maintained the BMD gains 5 years after a single zoledronate infusion with no additional treatment. Whether these results are also applicable to patients treated with denosumab for longer periods remains to be established.Metabolic health: pathophysiological trajectories and therap

The intriguing connections of leptin to hyperparathyroidism

Purpose: Leptin has been implicated in bone metabolism, but the association with parathyroid gland function has not been fully clarified. This review aimed to summarize evidence of the association between leptin and hyperparathyroidism, both primary and secondary, elucidating the potential pathophysiologic and therapeutic consequences between leptin and parathyroid hormone, hopefully prompting the design of new studies. Results: Experimental studies indicate a positive loop between leptin and parathyroid hormone in primary hyperparathyroidism. Dissimilar, parathyroid hormone seems to inhibit leptin expression in severe secondary hyperparathyroidism. Data from clinical studies indicate higher leptin levels in patients with primary hyperparathyroidism than controls, but no association between parathyroid hormone and leptin levels, as well as a minimal or neutral effect of parathyroidectomy on leptin levels in patients with primary hyperparathyroidism. Clinical data on secondary hyperparathyroidism, mainly derived from patients with chronic kidney disease, indicate a potential inverse association between leptin and parathyroid hormone in some, but not all studies. This relationship may be affected by the diversity of morbidity among these patients. Conclusions: Data from experimental studies suggest a different association between leptin and parathyroid hormone in primary and secondary hyperparathyroidism. Data from clinical studies are conflicting and potentially affected by confounders. More focused, well-designed studies are warranted to elucidate a potential association between leptin and parathyroid hormone, which may have specific clinical implications, i.e., targeting obesity and hyperleptinemia in patients with hyperparathyroidism. © 2017, Springer Science+Business Media, LLC

Combination and sequential treatment in women with postmenopausal osteoporosis

Introduction: Since postmenopausal osteoporosis is a chronic, potentially disabling condition requiring long-term treatment, the physician is expected to decide the optimal treatment strategy, e.g. how to use the available osteoanabolic and antiresorptive agents, sequentially or in combination, in the most effective and safe way, based on personalized patient care. Areas covered: Herein, the authors outline clinical data regarding the efficacy and safety of various sequential treatment strategies. More specifically, they compare the efficacy of osteoanabolic agents when they precede or follow antiresorptive treatment, as well as the efficacy of antiresorptives following other antiresorptives. Finally, the authors quote and discuss available evidence regarding the efficacy and safety of the co-administration of osteoanabolics and antiresorptives in comparison with monotherapies. Expert opinion: Initiation with an osteoanabolic agent followed by an antiresorptive seems to be the optimal treatment sequence, at least in patients with severe osteoporosis. Osteoanabolic treatment following antiresorptives seems to lead in more modest responses in bone mineral density (BMD) and bone turnover markers. Combination therapy with teriparatide and denosumab or zoledronate has achieved higher BMD gains compared to each agent alone; however, due to the high cost, combination therapy is rarely compensated. On the contrary, the combination of teriparatide with alendronate results in smaller BMD increases than TPTD monotherapy. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group

Off-label uses of denosumab in metabolic bone diseases

Denosumab (Dmab), a monoclonal antibody against the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) which substantially suppresses osteoclast activity, has been approved for the treatment of common metabolic bone diseases, including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis, in which the pathway of the RANK/RANKL/osteoprotegerin is dysregulated. However, the imbalance of RANKL/RANK/osteoprotegerin is also implicated in the pathogenesis of several other rare metabolic bone diseases, including Juvenile Paget disease, fibrous dysplasia, Hajdu Cheney syndrome and Langerhans cell histiocytosis, thus rendering Dmab a potential treatment option for these diseases. Dmab has been also administered off-label in selected patients (e.g., with Paget's disease, osteogenesis imperfecta, aneurysmal bone cysts) due to contraindications or unresponsiveness to standard treatment, such as bisphosphonates. Moreover, Dmab was administered to improve hypercalcemia induced by various diseases, including primary hyperparathyroidism, tuberculosis and immobilization. The aim of this review is to summarize existing evidence on off-label uses of Dmab in metabolic bone diseases and provide opinion for or against its use, which should be always considered on an individual basis. © 2019 Elsevier Inc

Selenium and selenoprotein P in nonalcoholic fatty liver disease

Conflicting data link nonalcoholic fatty liver disease (NAFLD), a disease with no currently approved treatment, with selenium (Se) and selenoprotein P (SELENOP), a glycoprotein synthesized and primarily secreted by the hepatocytes, functioning as a Se transporter from the liver to other tissues. This review aims to summarize the evidence between Se, SELENOP, and NAFLD, which may hopefully clarify whether current data on Se and SELENOP in NAFLD warrant further investigation for their diagnostic and therapeutic potential. Most, albeit not all, experimental data show a favorable effect of Se on hepatic steatosis, inflammation, and fibrosis. It seems that Se may exert an antioxidant effect on the liver, at least partly via increasing the activity of glutathione peroxidase, whose depletion contributes to the pathogenesis of hepatic inflammation and fibrosis. Se may also affect metalloproteinases, cytokines, and growth factors participating in the pathogenesis of NAFLD and, most importantly, may induce the apoptosis of hepatic stellate cells, the key players in hepatic fibrosis. However, the association between Se or SELENOP and insulin resistance, which is a principal pathogenetic factor of NAFLD, remains inconclusive. Clinical studies on Se or SELENOP in NAFLD are conflicting, apart from those in advanced liver disease (cirrhosis or hepatocellular carcinoma), in which lower circulating Se and SELENOP are constant findings. Existing data warrant further mechanistic studies in valid animal models of human NAFLD. Prospective cohort studies and possibly randomized controlled trials are also needed to elucidate the diagnostic and therapeutic potential of Se supplementation in selected NAFLD individuals with Se deficiency. © 2019, Hellenic Endocrine Society

Rock Samphire, a Candidate Crop for Saline Agriculture: Cropping Practices, Chemical Composition and Health Effects

The recent market trends for functional healthy foods have rekindled the interest in wild edible species and created a market niche for high added value products. The current supply, mainly supported by plants collected from the wild, cannot meet increasing market needs; therefore, it is of major importance to establish cropping protocols and further valorize wild plants for culinary and industrial applications. Sea fennel is a wild edible halophyte that is an important ingredient in local cuisines and is also used in folk medicine for its beneficial health effects. Its valorization has not been commercially explored on a great scale and more efforts are needed to integrate the species in farming systems. The present review compiles the most recent reports regarding the farming practices that could allow for the establishment of cultivation protocols for farmers, while the main constraints that hinder the further exploitation of the species are also presented. Moreover, this review presents the most up-to-date information regarding the chemical composition (e.g., chemical composition of the aerial parts and volatile compounds in essential oils) and the health-related effects of various plant parts (e.g., antimicrobial, insecticidal and anticholinesterase activities) aiming to reveal possible alternative uses that will increase the added value of the species and will contribute to its commercial exploitation. Finally, the future remarks and the guidelines that have to be followed are also discussed. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Pagets disease of bone and calcium homeostasis: Focus on bisphosphonate treatment

Pagets disease of bone (PDB) is the second most common metabolic bone disease. Bisphosphonates (BPs) are currently the drugs of choice for PDB. PDB and osteomalacia are both common in the elderly. The concept of relative vitamin D deficiency in patients with PDB was suggested long ago, but it has not yet elucidated. Both diseases predispose to fractures, but their combined action to fragility has not been studied yet. The older BPs, mainly etidronate, further inhibit bone mineralization. Mineralization defects have also been described in patients with PDB treated with pamidronate. Moreover, hypocalcemia and secondary hyperparathyroidism after treatment with BPs have been described in PDB. Hypocalcemia seems to be more severe after treatment with the more potent, intravenous zoledronic acid, which is currently the treatment of choice for PDB. The counteracting hyperparathyroidism pathophysiologically intends to increase renal reabsorption of calcium and 1.25-dihydroxy vitamin D production and to stimulate osteoclasts in order to prevent long-term hypocalcemia. However, the effect of PTH on osteoclasts is, at least partly, restricted in patients taking BPs. Secondary hyperparathyroidism is a potentially detrimental condition, especially in patients already suffering from another bone disease. Serum calcium and vitamin D deficiency should be restored before BP treatment and calcium and vitamin D administration should be possibly continued for longer after achieving normocalcemia, which may shorten the duration of secondary hyperparathyroidism. Quick summary: Mineralization defects and hypocalcemia with secondary hyperparathyroidism have been described in patients with Pagets disease of bone treated with bisphosphonates. Secondary hyperparathyroidism may be a potentially detrimental condition for patients with Pagets disease of bone. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart - New York