SCORE, OST and ORAI risk assessment tools could reduce the cost burden of BMD tests by selecting the high risk patients to osteoporosis. In this study we compared the ability of these risk assessment measures to assess probability of the osteoporosis among post-menopausal women.

There is a high prevalence of chronic hyponatremia in the elderly, frequently owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Recent reports have shown that even mild hyponatremia is associated with impaired gait stability and increased falls. An increased risk of falls among elderly hyponatremic patients represents a risk factor for fractures, which would be further amplified if hyponatremia also contributed metabolically to bone loss. To evaluate this possibility, we studied a rat model of SIADH and analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). In rats, dual-energy X-ray absorptiometry (DXA) analysis of excised femurs established that hyponatremia for 3 months significantly reduced bone mineral density by approximately 30% compared with normonatremic control rats. Moreover, micro-computed tomography (microCT) and histomorphometric analyses indicated that hyponatremia markedly reduced both trabecular and cortical bone via increased bone resorption and decreased bone formation. Analysis of data from adults in NHANES III by linear regression models showed that mild hyponatremia is associated with increased odds of osteoporosis (T-score -2.5 or less) at the hip [odds ratio (OR) = 2.85; 95% confidence interval (CI) 1.03-7.86; p < .01]; all models were adjusted for age, sex, race, body mass index (BMI), physical activity, history of diuretic use, history of smoking, and serum 25-hydroxyvitamin D [25(OH)D] levels. Our results represent the first demonstration that chronic hyponatremia causes a substantial reduction of bone mass. Cross-sectional human data showing that hyponatremia is associated with significantly increased odds of osteoporosis are consistent with the experimental data in rodents. Our combined results suggest that bone quality should be assessed in all patients with chronic hyponatremia.

No abstract available

The effectiveness of exercise for improving osteoporosis and fall prevention in patients diagnosed with osteoporosis or osteopenia has not been fully summarized. The Korean Society for Bone and Mineral Research and the Korean Society of Exercise Physiology has developed exercise guidelines for patients with osteoporosis or osteopenia and provide evidence-based recommendations.

To compare Predictive Index for Osteoporosis (PIO) with Osteoporosis Self-Assessment Tool for Asians (OSTA) as a clinical tool for identifying the risk of osteoporosis in Filipino men 50-69 and Filipino women 50-65 years of age.

The study of epigenetics reaches its 50th anniversary, however, its clinical application is gradually coming into the clinical setting. Osteoporosis is one of the major and widely diffused bone diseases. Pathogenic mechanisms at the epigenetic level may interfere with bone remodeling occurring during osteoporosis. Preclinical models were used to understand whether such events may interfere with the disease. Besides, observational clinical trials investigated epigenetic-related biomarkers. This effort leads to some epigenetic-related therapies in clinical trials for the treatment of osteoporosis. Bisphosphonates (BPs), target therapy blocking RANK/RANKL pathway, and anti-sclerostin antibody (SOST) are the main therapeutic approaches. However, future large trials will reveal whether epigenetic therapies of osteoporosis will remain a work in progress or data will become more robust in the real-world management of these frailty patients.

Osteoporosis is the most common disease involving bone degeneration. Current clinical treatments are not able to offer a satisfying curative effect, so the development of effective treatments is desired. Gene silencing through siRNA delivery has gained great attention as a potential treatment in bone diseases. SOST gene inhibits the Wnt signaling pathway reducing osteoblast differentiation. Consequently, silencing SOST genes with a specific siRNA could be a potential option to treat osteoporosis. Generally, siRNAs have a very short half-life and poor transfection capacity, so an effective carrier is needed. In particular, mesoporous silica nanoparticles (MSNs) have attracted great attention for intracellular delivery of nucleic acids. We took advantage of their high loading capacity to further load the pores with osteostatin, an osteogenic peptide. In this study, we developed a system based on MSNs coated with poly(ethylenimine), which can effectively deliver SOST siRNA and osteostatin inside cells, with the consequent augmentation of osteogenic markers with a synergistic effect. This established the potential utility of MSNs to co-deliver both biomolecules to promote bone formation, this being a potential alternative to treat osteoporosis.

No abstract available

Bisphosphonates are non-biodegradable compounds characterized by a phosphorus-carbon-phosphorus bond. By substituting the hydrogens on the carbon atom, a variety of bisphosphonates can be synthesized, each with distinct physical-chemical, biologic, therapeutic, and toxicologic characteristics. Bisphosphonates have in general a strong affinity to calcium phosphates, both in vitro and in vivo. They inhibit bone resorption through a cellular mechanism that is not yet completely understood. When given in large amounts, some bisphosphonates can inhibit normal and ectopic mineralization through a physical-chemical mechanism. The main difference among the various compounds appears to be their potency in inhibiting bone resorption, which can vary from 1 to 10,000. The potential efficacy of bisphosphonates in osteoporosis has been investigated extensively in animals. In the growing rat, they induce an increase in intestinal absorption and body retention of calcium. Various types of experimental osteoporosis, such as induced by immobilization, ovariectomy, administration of corticosteroids, or low calcium diet, can be prevented. Bisphosphonates are rapidly cleared from plasma, with 20%-60% deposited in bone and the remainder excreted in the urine. The half-life in bone is, however, very long. The toxicity of bisphosphonates is low, probably because of their rapid plasma and soft tissue clearance. It varies greatly from compound to compound. Bisphosphonates are used successfully in diseases with increased bone turnover, such as Paget's disease of bone, tumoral bone disease, and recently, osteoporosis. Most results in osteoporosis have been obtained with etidronate and pamidronate. Both of these compounds, as well as other bisphosphonates, such as tiludronate, alendronate, and clodronate, inhibit bone loss and sometimes even increase bone mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Obesity and osteoporosis have become major global health problems over the last decades as their prevalence is increasing. The interaction between obesity and bone metabolism is complex and not fully understood. Historically, obesity was thought to be protective against osteoporosis;however, several studies have challenged this belief. Even though the majority of the studies suggest that obesity has a favourable effect on bone density, it is unclear what the effect of obesity is on skeletal microarchitecture. Additionally, the effects of obesity on skeletal strength might be site-dependent as obese individuals are at higher risk of certain fractures. Several mechanical, biochemical and hormonal mechanisms have been proposed to explain the association between the adipose tissue and bone. Mechanical loading has positive effects on bone health, but this may not suffice in obesity. Low-grade systemic inflammation is probably harmful to the bone and increased bone marrow adipogenesis may lead to decreased bone mass in obese individuals. Finally, visceral abdominal fat may exert different actions to the bone compared with the subcutaneous fat. Achieving a better understanding of the association between adipose and bone tissue may help to identify new molecular therapeutic targets that will promote osteoblastic activity and/or inhibit adipogenesis and osteoclastic activity.

Thyroid hormones are essential for normal skeletal development and normal bone metabolism in adults but can have detrimental effects on bone structures in states of thyroid dysfunction. Untreated severe hyperthyroidism influences the degree of bone mass and increases the probability of high bone turnover osteoporosis. Subclinical hyperthyroidism, defined as low thyrotropin (TSH) and free hormones within the reference range, is a subtler disease, often asymptomatic, and the diagnosis is incidentally made during screening exams. However, more recent data suggest that this clinical condition may affect bone metabolism resulting in decreased bone mineral density (BMD) and increased risk of fracture, particularly in postmenopausal women. The main causes of exogenous subclinical hyperthyroidism are inappropriate replacement dose of thyroxin and TSH suppressive L-thyroxine doses in the therapy of benign thyroid nodules and thyroid carcinoma. Available data similarly suggest that a long-term TSH suppressive dose of thyroxin may decrease BMD and may induce an increased risk of fracture. These effects are particularly observed in postmenopausal women but are less evident in premenopausal women. Overt hypothyroidism is known to lower bone turnover by reducing both osteoclastic bone resorption and osteoblastic activity. These changes in bone metabolism would result in an increase in bone mineralization. At the moment, there are no clear data that demonstrate any relationship between BMD in adults and hypothyroidism. Despite these clinical evidences, the cellular and molecular actions of thyroid hormones on bone structures are not complete clear.

Osteoporosis (OP) is a common serious skeletal disorder marked by increased risk of bone fracture due to fragility. OP has been taken to be a disease linked with abnormal calcium metabolism that alone is obviously insufficient to explain the development of OP. Iron overload has been associated with the development of OP and increasing studies have suggested the association. However, direct evidence for this has not been clinically established. To this end, using the Roche biochemical autoanalyzer, we detected the concentration of iron, soluble transferrin receptor 2 (TFR2), and hepcidin, a key peptide regulating iron homeostasis, in the sera from patients with OP. It was shown that the iron and TFR2 concentration was markedly higher than that of healthy control; whereas the concentration of hepcidin was markedly lower than that in control. In addition, to pilot explore the underlying mechanism by which hepcidin was downregulated, we present that hepcidin can directly interact with TFR2 using immunoprecipitation. The present study first established the direct biochemical evidence for the involvement of hepcidin in the pathogenesis of OP, indicating that the upregulation of hepcidin could be used as a novel alternative therapeutic strategy in the management of OP.

Romosozumab, a specific inhibitor of sclerostin, is a unique approach to therapy for postmenopausal osteoporosis and related disorders. The elucidation of sclerostin deficiency as the molecular defect of syndromes of high bone mass with normal quality, and the pivotal role of sclerostin as a mediator of osteoblastic activity and bone formation, provided the platform for the evaluation of inhibitors of sclerostin to activate bone formation. An extensive preclinical program and 2 large fracture endpoint trials with romosozumab, a sclerostin-binding antibody, have been completed. This review will highlight the results of those studies and describe the current status of romosozumab as a potential therapy for osteoporosis.

Osteoporosis and osteopenia are diagnosed most commonly by evaluating the lowest T-score of BMD measurements, typically taken at three sites: the L1-L4 lumbar spine, femoral neck, and total hip. This study aimed to evaluate the effect of using all three BMD measurements and multivariate statistical theory to evaluate how the diagnoses of osteoporosis and osteopenia change in simulation studies and in real data. First, it was found that the T-scores from these three BMD measurements rarely give concordant diagnoses using the same World Health Organization (WHO) and International Society for Clinical Densitometry (ISCD) guidelines, so that the diagnosis strongly depends on the BMD sites measured. Next, strong correlations were found between the BMD measurements at different sites within the same person, which resulted in increased congruence/concordance between the diagnoses obtained from the BMD T-scores. Multivariate statistical theory was used to show that the joint distribution of the BMD T-scores at different sites follows a multivariate t distribution and found that the marginal distribution of any BMD T-score follows a univariate t distribution. Confidence ellipsoids were derived that are equivalent to the univariate WHO/ISCD thresholds for osteoporosis (T-score ≤-2.5) and osteopenia (-2.5 < T-score <-1). The study found that more patients are diagnosed with osteoporosis using the multivariate version of the WHO/ISCD guidelines rather than the current WHO/ISCD guidelines in both real data and simulation studies. Diagnoses of osteoporosis using the statistics derived method were also associated with higher FRAX (fracture risk assessment tool) probabilities of major osteoporotic (p = 0.001) and hip fractures (p = 2.2 × 10-6). In conclusion, this study shows that considering all three BMD T-scores is potentially more informative than using the single lowest BMD T-score. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Pharmacological and genetic studies over the past decade have established the follicle-stimulating hormone (FSH) as an actionable target for diseases affecting millions, namely osteoporosis, obesity, and Alzheimer's disease. Blocking FSH action prevents bone loss, fat gain, and neurodegeneration in mice. We recently developed a first-in-class, humanized, epitope-specific FSH-blocking antibody, MS-Hu6, with a KD of 7.52 nM. Using a Good Laboratory Practice (GLP)-compliant platform, we now report the efficacy of MS-Hu6 in preventing and treating osteoporosis in mice and parameters of acute safety in monkeys. Biodistribution studies using 89Zr-labeled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone and bone marrow. The MS-Hu6 displayed a β phase t½ of 7.5 days (180 hr) in humanized Tg32 mice. We tested 217 variations of excipients using the protein thermal shift assay to generate a final formulation that rendered MS-Hu6 stable in solution upon freeze-thaw and at different temperatures, with minimal aggregation, and without self-, cross-, or hydrophobic interactions or appreciable binding to relevant human antigens. The MS-Hu6 showed the same level of "humanness" as human IgG1 in silico and was non-immunogenic in ELISpot assays for IL-2 and IFN-γ in human peripheral blood mononuclear cell cultures. We conclude that MS-Hu6 is efficacious, durable, and manufacturable, and is therefore poised for future human testing.

Physiological circadian (ie, 24-hour) rhythms are critical for bone health. Animal studies have shown that genes involved in the intrinsic molecular clock demonstrate potent circadian expression patterns in bone and that genetic disruption of these clock genes results in a disturbed bone structure and quality. More importantly, circulating markers of bone remodeling show diurnal variation in mice as well as humans, and circadian disruption by, eg, working night shifts is associated with the bone remodeling disorder osteoporosis. In this review, we provide an overview of the current literature on rhythmic bone remodeling and its underlying mechanisms and identify critical knowledge gaps. In addition, we discuss novel (chrono)therapeutic strategies to reduce osteoporosis by utilizing our knowledge on circadian regulation of bone. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

We used an ovariectomy (OVX) rat model to test whether yeast hydrolysate (YH) has therapeutic effects on postmenopausal osteoporosis-induced bone loss. The rats were separated into five treatment groups: the sham group (sham operation); the control group (no treatment after OVX); the estrogen group (estrogen treatment after OVX); YH 0.5% group (drinking water supplementation with 0.5% YH after OVX); and the YH 1% group (drinking water supplementation with 1% YH after OVX). In addition, the YH treatment restored serum testosterone concentration in the OVX rats up to the normal level. Further, YH treatment affected bone markers; a significant increase in serum calcium concentration was observed after adding YH to the diet. The levels of serum alkaline phosphatase, osteocalcin, and cross-linked telopeptides of type I collagen were reduced by YH supplementation, unlike those in the no-treatment control. Although not statistically significant, YH treatment in OVX rats improved trabecular bone microarchitecture parameters. These results show that YH may ameliorate the bone loss caused by postmenopausal osteoporosis because of the normalization of serum testosterone concentration.

Osteoporosis is a disease of bone metabolism in which bisphosphonates (BPS) are the most common medications used in its treatment, whose main objective is to reduce the risk of fractures. The aim of this study was to conduct a systematic review on BPs adherence for treatment of osteoporosis.

Osteoporosis is a systemic skeletal disorder, characterized by reduced bone mass, deterioration of bone structure, increased bone fragility, and increased fracture risk. It is more frequent to find among women than men at a 4:1 ratio. Evidence suggests that to adopt changes on some life habits can prevent or delay development of osteoporosis. Several osteoporosis-risk factors have been confirmed in the US and western Europe, but in El Salvador there are neither reliable epidemiological statistics about this skeletal disorder nor studies addressing osteoporosis-risk factors in women. The aim of this study was to determinate the extent of osteoporosis knowledge, the levels of both daily calcium intake and weight-bearing physical activity, and the influence of several osteoporosis-risk factors on these variables in three age groups of Salvadorean women.

A systemic skeletal disease is characterized by low bone mass and micro-architectural deterioration with a consequent increase in bone fragility and susceptibility to fracture. Asia has the highest increment in the elderly population; therefore, osteoporotic fracture should be a noticeable health issue. The incidence rate of hip fractures in Asia could rise to 45% by the year 2050. Complementary and alternative medicine (CAM) is a group of various medical and health care systems, practices, and products that are not presently considered as part of formal medicine. CAMs have been described as "diagnosis, treatment, and/or prevention which complements mainstream medicine as a holistic, subjective and various natural approaches to medical problems by contributing to a common whole, satisfying claims not met by orthodoxy, or diversifying the conceptual frameworks of medicine".