Journal of Bone and Mineral Metabolism最新文献

Positive regulators of bone formation, such as mechanical loading and PTH, stimulate and negative regulators, such as aging and glucocorticoid excess, suppress IL-11 gene transcription in osteoblastic cells. Signal transduction from mechanical loading and PTH stimulation involves two pathways: one is Ca²⁺-ERK-CREB pathway which facilitates binding of ∆FosB/JunD to the AP-1 site to enhance IL-11 gene transcription, and the other is Smad1/5 phosphorylation that promotes IL-11 gene transcription via SBE binding and complex formation with ∆FosB/JunD. The increased IL-11 suppresses Sost expression via IL-11Rα-STAT1/3-HDAC4/5 pathway and enhances Wnt signaling in the bone to stimulate bone formation. Thus, IL-11 mediates stimulatory and inhibitory signals of bone formation by affecting Wnt signaling. Physiologically important stimulation of bone formation is exercise-induced mechanical loading, but exercise simultaneously requires energy source for muscle contraction. Exercise-induced stimulation of IL-11 expression in the bone increases the secretion of IL-11 from the bone. The increased circulating IL-11 acts like a hormone to enhance adipolysis as an energy source with a reduction in adipogenic differentiation via a suppression of Dkk1/2 expression in the adipose tissue. Such bone-fat linkage can be a mechanism whereby exercise increases bone mass and, at the same time, maintains energy supply from the adipose tissue.

The kidneys play an important role in the regulation of phosphate and calcium balance and serum concentrations, coordinated by fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25D). In patients with chronic kidney disease (CKD), this regulation is impaired, leading to CKD-mineral and bone disorder (CKD-MBD), characterized by decreased 1,25D, elevated FGF23, secondary hyperparathyroidism, hyperphosphatemia, bone abnormalities, and vascular and soft-tissue calcification. While bone abnormalities associated with CKD-MBD, known as renal osteodystrophy, have been recognized as the most typical interaction between the kidney and bone, a number of other kidney-bone interactions have been identified, for which our knowledge of the pathogenesis of CKD-MBD has played an important role. This article summarizes recent findings on CKD-MBD and explores the crosstalk between the kidney and bone from the perspective of CKD-MBD.

The primary sensory neurons involved in pain perception express various types of receptor-type ion channels at their nerve endings. These molecules are responsible for triggering neuronal excitation, translating environmental stimuli into pain signals. Recent studies have shown that acute nociception, induced by neuronal excitation, not only serves as a sensor for signaling life-threatening situations but also modulates our pathophysiological conditions. This modulation occurs through the release of neuropeptides by primary sensory neurons excited by nociceptive stimuli, which directly or indirectly affect peripheral systems, including immune function. Senso-immunology, an emerging research field, integrates interdisciplinary studies of pain and immunology and has garnered increasing attention in recent years. This review provides an overview of the systemic pathophysiological functions regulated by receptor-type ion channels, such as transient receptor potential (TRP) channels in primary sensory neurons, from the perspective of senso-immunology.

Bone functions not only as a critical element of the musculoskeletal system but also serves as the primary lymphoid organ harboring hematopoietic stem cells (HSCs) and immune progenitor cells. The interdisciplinary field of osteoimmunology has illuminated the dynamic interactions between the skeletal and immune systems, vital for the maintenance of skeletal tissue homeostasis and the pathogenesis of immune and skeletal diseases. Aberrant immune activation stimulates bone cells such as osteoclasts and osteoblasts, disturbing the bone remodeling and leading to skeletal disorders as seen in autoimmune diseases like rheumatoid arthritis. On the other hand, intricate multicellular network within the bone marrow creates a specialized microenvironment essential for the maintenance and differentiation of HSCs and the progeny. Dysregulation of immune-bone crosstalk in the bone marrow environment can trigger tumorigenesis and exacerbated inflammation. A comprehensive deciphering of the complex "immune-bone crosstalk" leads to a deeper understanding of the pathogenesis of immune diseases as well as skeletal diseases, and might provide insight into potential therapeutic approaches.

Introduction

Osteoporosis is a significant health concern characterized by weak and porous bones, particularly affecting menopausal women aged 50 and above, leading to increased risk of hip fractures and associated morbidity and mortality.

Materials and Methods

We conducted a study to assess the efficacy of single-strain versus mixed-strain probiotic supplementation on bone health using an ovariectomy (OVX) rat model of induced bone loss. The probiotics evaluated were Lactobacillus helveticus (L. helveticus), Bifidobacterium longum (B. longum), and a combination of both. Rats were divided into five groups: SHAM (Control negative), OVX (Control positive), OVX +L. helveticus, OVX + B. longum, and OVX + mixed L. helveticus and B. longum. Daily oral administration of probiotics at 10^8-10^9 CFU/mL began two weeks post-surgery and continued for 16 weeks.

Results

Both single-strain and mixed-strain probiotic supplementation upregulated expression of osteoblastic genes (BMP- 2, RUNX-2, OSX), increased serum osteocalcin (OC) levels, and improved bone formation parameters. Serum C-terminal telopeptide (CTX) levels and bone resorption parameters were reduced. However, the single-strain supplementation demonstrated superior efficacy compared to the mixed-strain approach.

Conclusion

Supplementation with B. longum and L. helveticus significantly reduces bone resorption and improves bone health in OVX rats, with single-strain supplementation showing greater efficacy compared to a mixed-strain combination. These findings highlight the potential of probiotics as a therapeutic intervention for osteoporosis, warranting further investigation in human studies.

Introduction: This study is to investigate the relation between serum dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) levels and the risk of osteoporosis in patients with T2DM.

Materials and methods: This cross-sectional study involved 938 hospitalized patients with T2DM. Linear regression models were used to explore the relationship between DHEA and DHEAS and the BMD at different skeletal sites. Multinominal logistic regression models and the restricted cubic spline (RCS) were used to evaluate the associations of DHEA and DHEAS with the risks of osteopenia and/or osteoporosis.

Results: In postmenopausal women with T2DM, after adjustment for confounders including testosterone and estradiol, DHEA showed a significant positive correlation with lumbar spine BMD (P = 0.013). Moreover, DHEAS exhibited significant positive correlations with BMD at three skeletal sites: including femoral neck, total hip, and lumbar spine (all P < 0.05). Low DHEA and DHEAS levels were associated with increased risk of osteopenia and/or osteoporosis (all P < 0.05) and the risk of osteoporosis gradually decreased with increasing DHEAS levels (P overall = 0.018, P-nonlinear = 0.559). However, DHEA and DHEAS levels in men over the age of 50 with T2DM were not associated with any of above outcomes.

Conclusion: In patients with T2DM, independent of testosterone and estradiol, higher DHEA and DHEAS levels are associated with higher BMD and lower risk of osteopenia/osteoporosis in postmenopausal women but not men over the age of 50.

Introduction: This study aimed to assess the effectiveness of calcimimetics in reducing the risk of fractures in dialysis patients with secondary hyperparathyroidism (SHPT).

Material and methods: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane Library for articles published through December 9, 2023. The quality of each trial was evaluated using the Cochrane Collaboration tool. Meta-analysis was performed using a random-effects model, and effect measures across studies were synthesized. The risk ratio (RR) and 95% confidence interval (CI) were used to quantify the risk of fracture.

Results: We identified seven studies involving 6481 dialysis patients with SHPT. The administration of calcimimetics reduced fracture incidence compared to placebo or conventional treatment (RR: 0.50, 95% CI 0.29-0.88, p = 0.02). Calcimimetics demonstrated a low number needed to treat (NNT) to prevent an incident fracture (NNT: 47).

Conclusion: The use of calcimimetics offers a significant benefit in reducing the risk of fractures in patients undergoing dialysis with SHPT.

Introduction: The effect of nutritional status on osteosarcopenia (OS) and major osteoporotic fracture (MOF) among the elderly is still unclear. So we aimed to compare the efficacy of the Mini-Nutrition Assessment-Short Form (MNA-sf), the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT) for predicting OS and MOF among the elderly.

Materials and methods: A total of 409 participants were enrolled in this prospective study. Blood biochemical indexes, nutritional status, and bone- and muscle-related examinations were assessed at initial visit to the outpatient. Participants were divided into 4 groups: (1) control; (2) osteopenia/osteoporosis; (3) sarcopenia; (4) osteosarcopenia, and then followed for 5 years, recording the occurrence time of MOF.

Results: The frequency values of osteopenia/osteoporosis, sarcopenia, and OS, at baseline, were respectively 13.4, 16.1, and 12% among the study samples. Correlation analysis showed that nutritional status scores were associated with body mass index, handgrip strength, albumin, bone mineral density, and physical functions. According to multivariate models, poor nutritional status was significantly associated with a higher risk of OS and MOF (P < 0.05). Survival analysis showed that the MOF rate in malnutrition group was significantly higher than normal nutrition group (P < 0.05). The receiver operator characteristic curve shows that the value of MNA-sf to diagnose OS and MOF is greater (P < 0.05).

Conclusion: The poor nutritional status was associated with a higher risk of both OS and MOF. MNA-sf showed a superior diagnostic power for OS and MOF among the elderly. Early nutrition assessments and interventions may be key strategies to prevent OS and fractures.

Introduction: The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ -2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis with teriparatide (TPTD) and alendronate (ALN), and to investigate the relationship with incident vertebral fracture by re-analyzing data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high fracture risk.

Materials and methods: Participants received sequential therapy with once-weekly TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group) or ALN monotherapy for 120 weeks (ALN group). BMDs were measured at the lumbar spine (L2-4), total hip, and femoral neck at 0, 24, 48, 72, and 120 weeks by dual-energy X-ray absorptiometry. The T2T goal was BMD ≥ -2.5 SD, and the endpoint was the proportion of participants with baseline BMD < -2.5 SD in three measurement sites achieving BMD ≥ -2.5 SD.

Results: A total of 559 participants were selected. BMD ≥ -2.5 SD at 120 weeks in the L2-4, total hip, and femoral neck sites was achieved in 20.5%, 23.1%, and 5.9%, respectively, in the TPTD-ALN group and 22.2%, 11.7%, and 7.3%, respectively, in the ALN group. Incident vertebral fractures occurred in areas of both lower and high BMD.

Conclusion: During the 1.5-year treatment period, more than 20% of participants achieved BMD ≥ -2.5 SD as a T2T goal at L2-4. Since the achievement level differed depending on the BMD measurement site, the appropriate site should be selected according to the baseline BMD level.