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Among postmenopausal women with osteoporosis and a high risk of fracture, treatment with the monoclonal antibody romosozumab for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate for 12 months followed by alendronate.

Romosozumab binds sclerostin, increases bone formation, and decreases bone resorption. Postmenopausal women with osteoporosis were assigned to romosozumab or placebo for 1 year, followed by 1 year of denosumab. Romosozumab was associated with lower vertebral and clinical fracture risk. Osteoporosis can lead to fragility fractures, which result in clinical burden and increased mortality. 1 , 2 Even after a fracture, fewer than 25% of patients receive pharmacologic treatment for osteoporosis. 3 – 5 After the discovery that sclerostin deficiency causes rare genetic conditions that are characterized by high bone mass and resistance to fracture, 6 , 7 sclerostin became a therapeutic target for the treatment of osteoporosis. Sclerostin, a negative regulator of bone formation that is secreted by osteocytes, 8 inhibits Wnt signaling, down-regulating this stimulus for osteoblast development and function. 9 Romosozumab (Amgen and UCB Pharma) is a monoclonal antibody that binds and inhibits sclerostin, with . . .

Summary We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80 % of her medication. Introduction Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers. Methods Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53–84 years), randomised to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for 2 years. The LSC for each marker was derived within the study population, whereas RIs were obtained from a control group of healthy premenopausal women (age 35–40 years). Results Over 70 % of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI −63 % (difference 13 %, 95 % CI 0 to 27.1, P  = 0.049) and good compliance −67 % (difference 15.9 %, 95 % CI 6.3 to 25.5, P  = 0.001). Responders had a greater increase in spine bone density compared to nonresponders; for example 6.2 vs. 2.3 % (difference 3.9 %, 95 % CI 1.6 to 6.3, P  = 0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate. Conclusions Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD, and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.

In this randomized trial, women 65 years of age or older who had osteopenia received four infusions of zoledronate or normal saline at 18-month intervals. Zoledronate was associated with a significantly lower risk of fragility fractures than placebo.

Pathological destructive bone diseases are primarily caused by the failure of a lifelong self‐renewal process of the skeletal system called bone remodelling. The mechanisms underlying this process include enhanced osteoclast activity and decreased generation of the osteoblast lineage. Intercellular interaction and crosstalk among these cell types are crucial for the maintenance of bone remodelling, either through the secretion of growth factors or direct cell–cell physical engagement. Recent studies have revealed that exosomes derived from bone cells, including osteoclasts, osteoblasts and their precursors, play pivotal roles on bone remodelling by transferring biologically active molecules to target cells, especially in the processes of osteoclast and osteoblast differentiation. Here, we review the contents of bone‐derived exosomes and their functions in the regulatory processes of differentiation and communication of osteoclasts and osteoblasts. In addition, we highlight the characteristics of microRNAs of bone‐derived exosomes involved in the regulation of bone remodelling, as well as the potential clinical applications of bone‐derived exosomes in bone remodelling disorders.

SummaryThyrotoxicosis leads to loss of bone mass. Vitamin D is important to bone health. In this randomized, placebo-controlled trial, we showed that bone restoration did not improve when adding vitamin D supplementation to standard care of Graves’ disease thyrotoxicosis. Bone density and microarchitecture improved markedly with treatment of thyrotoxicosis.PurposeVitamin D is important to skeletal health and ensuring a replete vitamin D status is recommended. In thyrotoxicosis, bone turnover is increased and bone mass density (BMD) reduced. We examined whether vitamin D supplementation improves bone recovery in thyrotoxicosis caused by Graves’ disease (GD).MethodsUsing a double-blinded design, hyperthyroid patients with GD were randomized to vitamin D3 70 µg/day (2800 IU) or similar placebo as add-on to antithyroid drugs (ATD). At baseline and 9 months, we measured BMD and bone architecture using DXA and high resolution peripheral quantitative computerized tomography. Bone turnover markers (BTM) were measured at 3 months also. Effect of vitamin D versus placebo and the response to ATD treatment were analyzed using linear mixed modelling.ResultsEighty-six GD patients were included (age 41 ± 14 years, 86% females). Compared to placebo, vitamin D3 did not improve BMD or microarchitecture. In response to ATD, BMD increased in the hip by 2% (95%CI: 1–4%). Cortical porosity decreased in tibia (− 7% [95%CI: − 12 to − 2%]) and radius [− 14% [95%CI: − 24 to − 3%]), and trabecular thickness increased (tibia (5% [95%CI: 2 − 9%]) and radius (4% [95%CI: 1–7%]). Changes in BTM, but not thyroid hormones, were associated with changes in BMD by DXA and with changes in the cortical compartment.ConclusionIn newly diagnosed GD, 9 months of high dose vitamin D3 supplementation does not offer benefit by improving skeletal health. Treatment of thyrotoxicosis is associated with the recovery of BMD and microarchitecture.Clinicaltrial.gov identifierNCT02384668

This study shows that in postmenopausal women with low bone mineral density, the monoclonal antibody romosozumab, which binds to sclerostin, an osteoblast-activity inhibitor, was associated with increased bone mineral density and bone formation and decreased bone resorption. Osteoporosis is characterized by low bone mass and defects in microarchitecture that are responsible for decreased bone strength and increased risk of fracture. 1 Antiresorptive drugs for osteoporosis increase bone mineral density and prevent the progression of structural damage but may not restore bone structure. Stimulation of bone formation is necessary to achieve improvements in bone mass, architecture, and strength. Sclerostin, encoded by the gene SOST, is an osteocyte-secreted glycoprotein that has been identified as a pivotal regulator of bone formation. By inhibiting the Wnt and bone morphogenetic protein signaling pathways, sclerostin impedes osteoblast proliferation and function, thereby decreasing bone formation. . . .

SummaryEarly PINP changes correlate with 18-month lumbar spine BMD changes and the correlation was greater with abaloparatide versus teriparatide. The uncoupling index was similar between the two agents.IntroductionWe evaluated the relationship between early PINP changes and subsequent changes in spine BMD following abaloparatide and teriparatide treatments. We also explored the use of an “uncoupling index” (UI), the balance between bone formation and bone resorption, which we hypothesised would be similar in response to these treatment groups.MethodsBlood samples were taken for measurement of bone turnover markers (BTMs) s-PINP and s-CTX at baseline, 1, 3, 6, 12, and 18 months from 189 abaloparatide patients and 227 teriparatide patients randomly selected from all participants who completed the study. BMD was measured by DXA at baseline, 6, 12, and 18 months. Correlations were calculated between log ratio of BTMs from baseline to 3 months and percent change from baseline in BMD at 18 months. A UI was calculated using log transformation and subtraction of the standard deviate for s-CTX from the standard deviate for s-PINP for each patient.ResultsEarly BTM changes were associated with subsequent BMD changes for both treatments. Pearson correlations for the log ratio of PINP over baseline at 3 months and BMD percent change from baseline at 18 months were larger (P < 0.0001) with abaloparatide (r = 0.561) than teriparatide (r = 0.198). The mean UI at 1 month was greater for abaloparatide versus teriparatide (1.743 and 1.493, respectively; P = 0.03) but was similar at 3 months or later time points.ConclusionsEarly s-PINP changes correlate with percentage change in lumbar spine BMD 18 months after treatment with both abaloparatide and teriparatide, though the correlation with abaloparatide was greater. The UI was similar between abaloparatide and teriparatide suggesting that the balance between formation and resorption markers was similar.

Temporomandibular joint (TMJ) osteoarthritis is a common chronic degenerative disease of the TMJ. In order to explore its aetiology and pathological mechanism, many animal models and cell models have been constructed to simulate the pathological process of TMJ osteoarthritis. The main pathological features of TMJ osteoarthritis include chondrocyte death, extracellular matrix (ECM) degradation and subchondral bone remodelling. Chondrocyte apoptosis accelerates the destruction of cartilage. However, autophagy has a protective effect on condylar chondrocytes. Degradation of ECM not only changes the properties of cartilage but also affects the phenotype of chondrocytes. The loss of subchondral bone in the early stages of TMJ osteoarthritis plays an aetiological role in the onset of osteoarthritis. In recent years, increasing evidence has suggested that chondrocyte hypertrophy and endochondral angiogenesis promote TMJ osteoarthritis. Hypertrophic chondrocytes secrete many factors that promote cartilage degeneration. These chondrocytes can further differentiate into osteoblasts and osteocytes and accelerate cartilage ossification. Intrachondral angiogenesis and neoneurogenesis are considered to be important triggers of arthralgia in TMJ osteoarthritis. Many molecular signalling pathways in endochondral osteogenesis are responsible for TMJ osteoarthritis. These latest discoveries in TMJ osteoarthritis have further enhanced the understanding of this disease and contributed to the development of molecular therapies. This paper summarizes recent cognition on the pathogenesis of TMJ osteoarthritis, focusing on the role of chondrocyte hypertrophy degeneration and cartilage angiogenesis.

Osteoporosis is a bone disease characterized by reduced bone mass, which leads to increased risk of bone fractures, and poses a significant risk to public health, especially in the elderly population. The traditional Chinese medicinal herb Epimedii has been utilized for centuries to treat bone fracture and bone loss. Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be the main bioactive component. This review provides a comprehensive survey of previous studies on icariin, including its structure and function, effect on bone metabolism, and potential for clinical application. These studies show that icariin promotes bone formation by stimulating osteogenic differentiation of BMSCs (bone marrow-derived mesenchymal stem cells), while inhibiting osteoclastogenic differentiation and the bone resorption activity of osteoclasts. Furthermore, icariin has been shown to be more potent than other flavonoid compounds in promoting osteogenic differentiation and maturation of osteoblasts. A 24-month randomized double-blind placebo-controlled clinical trial reported that icariin was effective in preventing postmenopausal osteoporosis with relatively low side effects. In conclusion, icariin may represent a class of flavonoids with bone-promoting activity, which could be used as potential treatment of postmenopausal osteoporosis.