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Purpose Many postmenopausal women desire non-pharmaceutical alternatives to hormone therapy for protection against osteoporosis. Soybean isoflavones, especially genistein, are being studied for this purpose. This study examined the effects of synthetic genistein in combination with other potential bone-protective dietary molecules on bone mineral density (BMD) in early postmenopausal women. Methods In this 6-month double-blind pilot study, 70 subjects were randomized to receive daily either calcium only or the geniVida™ bone blend (GBB), which consisted of genistein (30 mg/days), vitamin D3 (800 IU/days), vitamin K1 (150 μg/days) and polyunsaturated fatty acids (1 g polyunsaturated fatty acids as ethyl ester: eicosapentaenoic acid/docosahexaenoic acid ratio = ~2/1). Markers of bone resorption and formation and BMD at the femoral neck, lumbar spine, Ward’s triangle, trochanter and intertrochanter, total hip and whole body were assessed. Results Subjects supplemented with the GBB ( n  = 30) maintained femoral neck BMD, whereas in the placebo group ( n  = 28), BMD significantly decreased ( p  = 0.007). There was also a significant difference ( p  < 0.05) in BMD between the groups at Ward’s triangle in favor of the GBB group. Bone-specific alkaline phosphatase and N-telopeptide significantly increased in the GBB group in comparison with those in baseline and in the placebo group. The GBB was well tolerated, and there were no significant differences in adverse events between groups. Conclusions The GBB may help to prevent osteoporosis and reduce fracture risk, at least at the hip, in postmenopausal women. Larger and longer-term clinical trials are warranted.

Background Roux-en-Y gastric bypass (RYGB) surgery is the gold standard surgical treatment for obesity. However, unintended nutritional deficiencies following this surgery are common, including changes in bone metabolism. We assessed changes in bone mineral density (BMD), nutritional compounds, and bone resorption markers before and 1 year following RYGB surgery. Methods Our study included 22 female patients with class II/III obesity. A clinical questionnaire, a 24-h recall, blood and urine samples, and dual-energy X-ray absorptiometry were provided. Results Mean age was 37.2 ± 9.6 years; 86 % were Caucasian and 77.2 % were premenopausal. Mean preoperative body mass index was 44.4 ± 5.0 and 27.5 ± 4.5 kg/m 2 at 1-year follow-up ( p  < 0.001). 25-OH-vitamin D-levels were similar in both periods [11.7 (9.7–18.0) vs. 15.7 (10.2–2.7) pg/dL, p  = 0.327]. Serum N -telopeptide (16.3 ± 3.4 vs. 38.2 ± 7.0 nM BCE, p  < 0.001) and parathyroid hormone (45.4 ± 16.7 vs. 62.7 ± 28.9 pg/mL, p  = 0.026) increased after RYGB surgery, reflecting bone resorption. BMD decreased after RYGB surgery in the lumbar spine (1.13 ± 0.11 vs. 1.04 ± 0.09 g/cm 2 , p  = 0.001), femoral neck (1.03 ± 0.15 vs. 0.94 ± 0.16 g/cm 2 , p  = 0.001), and total femur (1.07 ± 0.11 vs. 0.97 ± 0.15 g/cm 2 , p  = 0.003). Conclusions Decreased BMD in the lumbar spine, femoral neck, and total femur is detectable in women 1 year after RYGB surgery. Calcium malabsorption, caused by vitamin D deficiency and increased bone resorption, is partially responsible for these outcomes and should be targeted in future clinical trials.

Acute spinal cord injury is associated with rapid bone loss and an increased risk of fracture. In this double-blind, randomized, placebo-controlled trial, 17 patients were followed for 1 year after administration of either 4 or 5 mg of zoledronic acid or placebo. Bone mineral density (BMD) and structural analyses of the proximal femur were performed using the hip structural analysis program at entry, 6 months, and 12 months. The 17 subjects completed 12 months of observation, nine receiving placebo and eight zoledronic acid. The placebo group showed a decrease in BMD, cross-sectional area, and section modulus and an increase in buckling ratio at each proximal femur site at 6 and 12 months. Six months after zoledronic acid, BMD, cross-sectional area, and section modulus increased at the femoral neck and intertrochanteric regions and buckling ratio decreased consistent with improved bone stability. However, at 12 months, the femoral narrow-neck values declined to baseline. In contrast to placebo, the intertrochanteric region and femur shaft were maintained at or near baseline through 12 months in the zoledronic acid-treated group. Urine N-telopeptide excretion was increased at baseline and declined in both the placebo and treatment groups during the 12 months of observation. We conclude that a single administration of zoledronic acid will ameliorate bone loss and maintain parameters of bone strength at the three proximal femur sites for 6 months and at the femur intertrochanteric and shaft sites for 12 months.

The aim of our study was to elucidate the pathophysiology of systemic sclerosis-related osteoporosis and the prevalence of vertebral fragility fracture in postmenopausal women with systemic sclerosis (SSc). Fifty-four postmenopausal women with scleroderma and 54 postmenopausal controls matched for age, BMI, and smoking habits were studied. BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline. All subjects had a spine X-ray to ascertain the presence of vertebral fractures. bone mineral density at lumbar spine (BMD 0.78±0.08 vs 0.88±0.07; p<0,001), femoral neck (BMD: 0.56±0.04 vs 0.72±0.07; p<0,001) and total femur (BMD: 0.57±0.04 vs 0.71±0.06; p<0,001) and ultrasound parameter at calcaneus (SI: 80.10±5.10 vs 94.80±6.10 p<0,001) were significantly lower in scleroderma compared with controls; bone turnover markers and parathyroid hormone level were significantly higher in scleroderma compared with controls, while serum of 25(OH)D3 was significantly lower. In scleroderma group the serum levels of 25(OH)D3 significantly correlated with PTH levels, BMD, stiffness index and bone turnover markers. One or more moderate or severe vertebral fractures were found in 13 patients with scleroderma, wherease in control group only one patient had a mild vertebral fracture. Our data shows, for the first time, that vertebral fractures are frequent in subjects with scleroderma, and suggest that lower levels of 25(OH)D3 may play a role in the risk of osteoporosis and vertebral fractures.

The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n  = 7), resistive exercise only (RE; n  = 8), or no exercise (control n  = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest ( p  ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6–24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control ( p  = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.

Insertion of a metallic implant into the femur changes bone loading conditions and results in remodeling of femoral bone. To quantify these changes in bone mineral density (BMD) after total hip arthroplasty, we monitored femoral bone with dual X-ray absorptiometry (DXA). The periprosthetic bone mineral density was measured in seven Gruen zones at scheduled time intervals during a 10-year follow-up. A total of 38 patients went through either cemented (n=13) or uncemented arthroplasty (n=25). During the 1st post-operative year BMD decreased markedly in both groups mainly in the calcar area (Gruen zone 7); 21.9 % in the uncemented group (p<0.005) and 26.1 % in the cemented group (p<0.005). After that there was a slight continuous BMD loss in the proximal part of the femur and a slight increase in the distal part of femur, especially after uncemented THA. In the non-operated control side, BMD showed only a slight decrease during the follow-up (0.9 %, p=0.003). The study shows that when a good prosthesis-bone integration with or without cement is achieved, remodeling of the periprosthetic bone decreases after the 1st post-operative year and the bone loss reflects merely normal ageing.

Autophagy may play an important role in the occurrence and development of glucocorticoid‐induced osteonecrosis of the femoral head (GC‐ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC‐ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC‐ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC‐induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC‐ONFH was used for evaluating the therapeutic effect of oral lithium on GC‐ONFH and underlying mechanism. Findings demonstrated that GC over‐activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over‐activated autophagy of GC‐treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC‐ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over‐activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up‐regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC‐ONFH. Lithium may be a promising therapeutic agent for GC‐ONFH. However, the role of autophagy in the pathogenesis of GC‐ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC‐ONFH, and the efficacy of lithium in the treatment of GC‐ONFH and its underlying mechanisms.

This study delved into the role of the PI3K/AKT signaling pathway and cuproptosis in steroid-induced osteonecrosis of the femoral head (SIONFH), assessing the therapeutic potential of the PI3K agonist 740Y-P. We analyzed femoral head specimens from SIONFH patients using DIA proteomics, identifying differentially expressed proteins linked to cuproptosis. In vitro, MC3T3-E1 cells treated with dexamethasone (DEX) exhibited hallmarks of cuproptosis, including downregulation of DLAT, PDHB, SLC25A3, and FDX1, increased copper ions, and reduced osteogenic potential, as shown by decreased ALP activity and RUNX2/BMP2 expression. The PI3K/AKT pathway’s modulation of FDX1 was key to cuproptosis regulation; activating it with 740Y-P restored FDX1 levels and partially recovered osteogenic capacity. An in vivo rat model of SIONFH treated with 740Y-P demonstrated improved bone parameters, reversed osteogenic suppression, and upregulated PI3K/AKT/FDX1 expression, validating the pathway’s role in cuproptosis and the agonist’s therapeutic potential for treating SIONFH and glucocorticoid-associated bone disorders.

Despite the widespread observations on the osteogenic effects of magnesium ion (Mg 2+ ), the diverse roles of Mg 2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg 2+ in bone repair. During the early inflammation phase, Mg 2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg 2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg 2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg 2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg 2+ . Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg 2+ in bone healing. Supplementation of magnesium (Mg2+) or its inclusion in biomaterials has beneficial effects for bone formation, but it has also been reported that it can have detrimental effects. Here, the authors analyse dose- and time-dependent effects of Mg2+ on bone regeneration and show that it can stimulate monocyte-macrophage lineage cells to support bone formation in the early phases of repair, but inhibit bone repair and mineralization in later stages by promoting a pro-inflammatory environment.

Objectives: To examine the effects of a simple and inexpensive physical activity intervention on change in bone mass and structure in school aged children. Methods: Fifty one children (n = 23 boys and 28 girls; mean age 10.1 years) participated in “Bounce at the Bell” which consisted of 10 counter-movement jumps 3× per day (total ∼3 min/day). Controls were 71 matched children who followed usual school practice. We assessed dietary calcium, physical activity, physical performance, and anthropometry in September and after 8 months of intervention (June). We measured bone mineral content (BMC) and bone area at the lumbar spine, total body, and proximal femur. Proximal femur scans were also analysed for bone geometry and structural strength using the hip structural analysis program. Lean and fat mass (g) were also calculated. Results: Groups were similar at baseline and did not differ in weight, height, total body, lumbar spine, proximal femur, or femoral neck BMC. Control children had a greater increase in adjusted total body BMC (1.4%). Intervention children gained significantly more BMC at the total proximal femur (2%) and the intertrochanteric region (27%). Change in bone structural parameters did not differ between groups. Conclusions: This novel, easily implemented exercise program, took only a few minutes each day and enhanced bone mass at the weight bearing proximal femur in early pubertal children. A large, randomised study of boys and girls should be undertaken powered to test the effectiveness of Bounce at the Bell in children at different stages of maturity, and in boys and girls independently.