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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.

Summary We report the results of alendronate ingestion plus exercise in preventing the declines in bone mass and strength and elevated levels of urinary calcium and bone resorption in astronauts during 5.5 months of spaceflight. Introduction This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long-duration spaceflight. Methods We report the results from seven International Space Station (ISS) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission. All crewmembers had available for exercise a treadmill, cycle ergometer, and a resistance exercise device. Our assessment included densitometry of multiple bone regions using X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and assays of biomarkers of bone metabolism. Results In addition to pre- and post-flight measurements, we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device, called the interim resistance exercise device, and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device (ARED). Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained. The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including: DXA-determined losses in bone mineral density of the spine, hip, and pelvis, QCT-determined compartmental losses in trabecular and cortical bone mass in the hip, calculated measures of fall and stance computed bone strength of the hip, elevated levels of bone resorption markers, and urinary excretion of calcium. Conclusions The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long-duration spaceflight.

Purpose Bone complications of metastatic disease, including skeletal-related events (SREs), impair patients' functioning and quality of life. In a randomized, phase 3 trial of 1,776 patients with metastases from solid tumors (except breast or prostate) or multiple myeloma, denosumab was non-inferior to zoledronic acid (ZA) in delaying or preventing SREs. This ad hoc analysis reports outcomes in the subgroup of 1,597 patients with solid tumors, excluding patients with multiple myeloma. Methods Patients received monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg, adjusted for creatinine clearance, with calcium and vitamin D supplementation recommended. Endpoints included times to first on-study SRE, first-and-subsequent SREs, and pain worsening. Results Denosumab significantly delayed time to first on-study SRE compared with ZA (HR, 0.81; 95 % CI, 0.68–0.96) and time to first-and-subsequent SREs (RR, 0.85; 95 % CI, 0.72–1.00). Denosumab also significantly delayed time to development of moderate or severe pain (HR, 0.81; 95 % CI, 0.66–1.00), pain worsening (HR, 0.83; 95 % CI, 0.71–0.97), and worsening pain interference in patients with no/mild baseline pain (HR, 0.77; 95 % CI, 0.61–0.96). Adverse event rates were 96 % in both groups. Grade 3 or 4 hypocalcemia, mostly without clinical sequelae, was more frequent in denosumab-treated patients (denosumab 4 %, ZA 2 %). Osteonecrosis of the jaw occurred infrequently (denosumab 0.8 %, ZA 1.1 %). Conclusions Denosumab was more effective in delaying or preventing SREs in patients with bone metastases from solid tumors and also prevented pain progression compared to ZA in this ad hoc analysis.

Postmenopausal osteoporosis (PMOP) is the most common type of osteoporosis. Numerous studies have shown that static magnetic fields (SMFs) can inhibit bone loss by regulating bone remodeling. However, there are currently no clinical studies on the treatment of osteoporosis with SMFs. This study aims to investigate the clinical therapeutic effects of moderate static magnetic fields (MMFs) on PMOP. In this paper, we constructed MMF device using neodymium-iron-boron (NdFeB) materials. At the animal level, the effect of MMF exposure for 8 weeks on estrogen deficiency-induced bone loss was investigated by evaluating bone microstructure, mechanical properties, and bone conversion using ovariectomized (OVX) mice. Clinically, a single-blind randomized controlled study in patients with PMOP was designed. PMOP patients aged 55-70 years were recruited and randomized into the control and MMF treatment groups. Clinical assessments of bone mineral density (BMD), bone turnover markers (BTMs) and VAS scores were performed at baseline and day 90, respectively. The results showed that MMF exposure significantly improved BMD, bone mineral content (BMC), bone microarchitecture and bone strength in OVX mice. For bone turnover, MMF increased the number of osteoblasts on the bone surface of OVX mice as well as the level of serum bone formation marker P1NP, while decreasing the number of osteoclasts and the level of serum bone resorption marker β-CTX. The clinical trial's results showed that MMF treatment had a positive effect on the improvement of BMD in the lumbar spine and increased serum P1NP levels while decreased β-CTX levels. In addition, MMF treatment decreased participants' VAS scores for low back pain. The results of both animal and clinical studies demonstrated that MMF treatment improved bone turnover and have a positive effect on BMD improvement, as well as alleviated low back pain in PMOP patients. This study will promote the translational research and clinical application of SMF treatment for osteoporosis. Intervention study of moderate static magnetic field on osteoporosis and iron metabolism in postmenopausal women, ChiCTR2100048604.

IntroductionTo investigate the effect of zoledronic acid on periprosthetic bone mineral density (BMD) and bone metabolism markers after primary total hip arthroplasty in females with postmenopausal osteoporosis.MethodsFrom November 2015 to April 2016, 40 female patients who met the inclusion criteria were randomized into two groups: a control group (calcium + calcitriol) and a zoledronic acid group (calcium + calcitriol + zoledronic acid). At 1 week and 3, 6, and 12 months after operation, BMD was obtained through dual-energy X-ray absorptiometry (DEXA). At pre-operation and at 3, 6, and 12 months after the operation, levels of bone metabolism markers were obtained by serum examination.ResultsLoss of BMD was significantly more pronounced in the control group than in the ZOL group in zones 1, 4, 6, and 7 at 6 months and in zones 1, 2, 4, 6, and 7 at 12 months after the operation. The levels of bone-resorption marker (β-CTX) were significantly lower in the ZOL group than in the control group at 3, 6, and 12 months after operation. The levels of bone-formation marker (TP1NP) performed statistically differences only at 12 months after the operation in these two groups.ConclusionsReceiving an intravenous infusion of 5 mg zoledronic acid after THA can effectively reduce periprosthetic BMD loss and improve bone remodeling in females with postmenopausal osteoporosis.SummaryZoledronic acid significantly inhibited bone mass loss in zones 1, 2, 4, 6, and 7 after THA and inhibited bone-resorption marker (β-CTX) to improve bone remodeling. Zoledronic acid treatment is potentially important for patients with osteoporosis after THA.

Cycling is recognised as a sport in which there is a high incidence of poor bone health. Sweat calcium losses may contribute to this. To examine whether a calcium-rich pre-exercise meal attenuates exercise-induced perturbations of bone calcium homeostasis caused by maintenance of sweat calcium losses. Using a randomized, counterbalanced crossover design, 32 well-trained female cyclists completed two 90 min cycling trials separated by 1 day. Exercise trials were preceded 2 hours by either a calcium-rich (1352 ± 53 mg calcium) dairy based meal (CAL) or a control meal (CON; 46 ± 7 mg calcium). Blood was sampled pre-trial; pre-exercise; and immediately, 40 min, 100 min and 190 min post-exercise. Blood was analysed for ionized calcium and biomarkers of bone resorption (Cross Linked C-Telopeptide of Type I Collagen (CTX-I), Cross Linked C-Telopeptide of Type II Collagen (CTX-II), Parathyroid Hormone (PTH), and bone formation (Procollagen I N-Terminal Propeptide (PINP)) using the established enzyme-linked immunosorbent assay technique. PTH and CTX-I increased from pre-exercise to post-exercise in both conditions but was attenuated in CAL (p < 0.001). PTH was 1.55 [1.20, 2.01] times lower in CAL immediately post-exercise and 1.45 [1.12, 1.88] times lower at 40 min post-exercise. CTX-I was 1.40 [1.15, 1.70] times lower in CAL at immediately post-exercise, 1.30 [1.07, 1.57] times lower at 40 min post-exercise and 1.22 [1.00, 1.48] times lower at 190 min post-exercise (p < 0.05). There was no significant interaction between pre-exercise meal condition and time point for CTX-II (p = 0.732) or PINP (p = 0.819). This study showed that a calcium-rich pre-exercise breakfast meal containing ~1350 mg of calcium consumed ~90 min before a prolonged and high intensity bout of stationary cycling attenuates the exercise induced rise in markers of bone resorption--PTH and CTX-I. Australian New Zealand Clinical Trials Registry ACTRN12614000675628.

SummaryTocotrienols have shown bone-protective effect in animals. This study showed that a 12-week tocotrienol supplementation decreased concentrations of bone resorption biomarker and bone remodeling regulators via suppressing oxidative stress in postmenopausal osteopenic women.IntroductionTocotrienols (TT) have been shown to benefit bone health in ovariectomized animals, a model of postmenopausal women. The purpose of this study was to evaluate the effect of 12-week TT supplementation on bone markers (serum bone-specific alkaline phosphatase (BALP), urine N-terminal telopeptide (NTX), serum soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and serum osteoprotegerin (OPG)), urine calcium, and an oxidative stress biomarker (8-hydroxy-2′-deoxyguanosine (8-OHdG)) in postmenopausal women with osteopenia.MethodsEighty-nine postmenopausal osteopenic women (59.7 ± 6.8 year, BMI 28.7 ± 5.7 kg/m2) were randomly assigned to three groups: (1) placebo (430 mg olive oil/day), (2) low TT (430 mg TT/day, 70% purity), and (3) high TT (860 mg TT/day, 70% purity). TT, an extract from annatto seed with 70% purity, consisted of 90% delta-TT and 10% gamma-TT. Overnight fasting blood and urine samples were collected at baseline, 6, and 12 weeks for biomarker analyses. Eighty-seven subjects completed the 12-week study.ResultsRelative to the placebo group, there were marginal decreases in serum BALP level in the TT-supplemented groups over the 12-week study period. Significant decreases in urine NTX levels, serum sRANKL, sRANKL/OPG ratio, and urine 8-OHdG concentrations and a significant increase in BALP/NTX ratio due to TT supplementation were observed. TT supplementation did not affect serum OPG concentrations or urine calcium levels throughout the study period. There were no significant differences in NTX level, BALP/NTX ratio, sRANKL level, and sRANKL/OPG ratio between low TT and high TT groups.ConclusionsTwelve-week annatto-extracted TT supplementation decreased bone resorption and improved bone turnover rate via suppressing bone remodeling regulators in postmenopausal women with osteopenia. Such osteoprotective TT’s effects may be, in part, mediated by an inhibition of oxidative stress.Trial registrationClinicalTrials.gov identifier: NCT02058420. Title: Tocotrienols and bone health of postmenopausal women.

Purpose Periacetabular bone loss poses a considerable challenge in the longevity and stability of acetabular implants used in total hip arthroplasty (THA). Innovations in implant design, specifically the introduction of three-dimensional (3D) porous titanium constructs, might reduce bone resorption. The purpose of this study was to build upon our previous randomized controlled trial, which found no change in periacetabular bone loss between a 3D porous none-hydroxyapatite coated titanium cup and a standard porous hydroxyapatite coated cup over a two year follow-up period by extending the follow-up duration to ten years post-surgery. Methods This was a single-centre, long-term follow-up study conducted over a ten year period in patients who had previously participated in a randomized controlled trial comparing a 3D porous titanium construct shell (PTC group) with a standard porous hydroxyapatite coated titanium shell (PC-group). The primary outcome measured was the change in bone mineral density (BMD) within four specific periacetabular zones, alongside overall bone loss, which was assessed through BMD in the lumbar spine at two, six and ten years postoperatively. Secondary outcomes included clinical outcome measures. Results In total, 18 in the PTC and 20 in the PC group were analysed for the primary endpoint up to ten years. The mean bone mineral density in zones 1–4 was 3.7% higher in the PTC group than in the PC group at six years postoperatively and 12.0% higher at ten years. Clinical outcomes, and the frequency of adverse events did not differ between the groups. Conclusions The PTC group displayed superior long-term bone preservation compared to the PC group while maintaining similar clinical outcomes up to ten years postoperatively. Although with a small sample size, our findings suggest that porous titanium cups have the potential to minimize BMD loss around the cup which could contribute to improving THA outcomes and implant durability.

Background/Objectives: Facial bone density, including the jawbone, declines earlier than that of the lumbar spine and calcaneus. Calcium maltobionate is reported to mitigate bone resorption and maintain bone density of the lumbar spine in post-menopausal women, but its effects on facial bone density remain understudied. Therefore, this study compared variations in facial bone mineral density with variations in calcaneal bone mineral density and bone resorption markers among healthy women, examining differences between pre- and post-menopause and the effects of continuous calcium maltobionate intake. Methods: This randomized, double-blind, placebo-controlled, parallel-group trial involved 48 healthy Japanese women aged 30–69 years, divided into two groups. The test food group received tablets containing calcium maltobionate, while the placebo group received tablets containing a maltose and calcium carbonate mixture for 24 weeks. Calcaneal and facial bone densities were measured pre- and post-intervention in both groups. Results: Post-intervention calcaneal bone mineral density and bone resorption marker deoxypyridinoline (DPD) showed no statistical difference between groups in pre-menopausal women. However, in post-menopausal women, the test food group exhibited significantly higher calcaneal bone density and lower DPD levels compared with the placebo group. Facial bone mineral density increased significantly in the test food group compared with the placebo group in post-menopausal participants, with similar trends observed in pre-menopausal participants. Conclusions: Facial bone mineral density could serve as a useful indicator for monitoring bone health from middle age onward. Moreover, continuous calcium maltobionate intake appears to mitigate bone density decline in pre- and post-menopausal women, contributing to osteoporosis prevention (UMIN-CTR ID: 000046391).

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate–carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate–carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate–carbonate dose; however, it raised the concentrations of phosphate and the Ca–phosphate product. The citrate–carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.