Efficacy of Rhizoma Drynariae (Drynaria roosii Nakaike) extracts in treating osteoporosis in rat models: A systematic review and meta-analysis.

ObjectiveIn this systematic review and meta-analysis, we aimed to evaluate the anti-osteoporotic efficacy of puerarin in rodent models of osteoporosis (OP) and to explore the impact of the dosage, treatment duration, and intervention method.MethodsA comprehensive search of electronic databases (e.g., PubMed, Embase, Web of Science, CNKI, and Wanfang) was conducted through August 2025. Randomized controlled trials investigating the effects of puerarin monotherapy on osteoporotic rats were included. The primary outcome measured was bone mineral density (BMD), and the secondary outcomes included bone histomorphometric parameters (BV/TV, Tb.Th, Tb.N, and Tb.Sp) and bone turnover markers (e.g., PINP, BALP, CTX, TRACP, and osteocalcin). Data were pooled using a random-effects model, and subgroup analyses were performed based on the puerarin dose, treatment duration, and intervention method. The study quality was assessed using the SYRCLE risk-of-bias tool.ResultsTwenty-eight studies involving 570 animals were included. The meta-analysis demonstrated that puerarin significantly increased femoral BMD (SMD = 2.95, 95% CI: 2.32 to 3.58, and p < 0.00001) and improved the bone microarchitecture by increasing BV/TV, Tb.Th, and Tb.N, and decreasing Tb.Sp. Subgroup analysis revealed that the most pronounced BMD improvement occurred at doses ≥50 mg/kg/day administered for ≥8 weeks. Puerarin significantly suppressed bone resorption markers, CTX and TRACP, and elevated serum levels of osteocalcin, calcium, and phosphorus. However, its effects on bone formation markers, PINP and BALP, were not statistically significant.ConclusionPuerarin exhibits significant therapeutic potential for OP in rat models by increasing BMD, improving bone quality, and rebalancing bone metabolism in favor of formation, primarily through the inhibition of resorption. The optimal effect appears to be dose- and duration-dependent. Although these preclinical findings are promising, the clinical translation of puerarin requires validation through larger-scale, high-quality animal studies and subsequent clinical trials.

Little research exists on the dynamic effects of glucocorticoids on bone mineral density (BMD) and microarchitecture of trabecular bones of rats assessed by micro-computed tomography (micro-CT). To investigate time-related changes in the BMD and microarchitecture of trabeculae in rats exposed to glucocorticoid. Female Sprague-Dawley rats were recruited into a baseline group, glucocorticoid-treated groups, or control groups. Glucocorticoid-treated rats were given daily subcutaneous injections of methylprednisolone at a dosage of 3.5 mg/kg for 1 or 9 weeks. A high-resolution micro-CT was used to identify the densitometric and microarchitectural properties of trabeculae in both the proximal metaphysis of tibiae and the sixth lumbar vertebrae (L6). Compared with baseline rats, volumetric BMD, tissue BMD, bone volume fraction, trabecular number, and degree of anisotropy of trabeculae from tibiae or L6 increased in control rats and glucocorticoid-treated rats with time; however, changes in the latter group were smaller. Compared with control rats at each time point, a decrease occurred in volumetric BMD, tissue BMD, bone volume fraction, trabecular number, degree of anisotropy, and trabecular connectivity density in trabecular bones from tibiae or L6 in glucocorticoid-treated rats. The decrease was greater in week 9 compared to week 1. Contrarily, an increase was noted in trabecular thickness, trabecular separation, and structure model index in glucocorticoid-treated rats. A time-related analysis within glucocorticoid-treated groups in both skeletal regions showed a decline in bone volume fraction, trabecular connectivity density, trabecular number, and degree of anisotropy with time, but trabecular thickness and trabecular separation were elevated. Methylprednisolone can inhibit bone mineralization and bone mass gain with growth in rats. It can also deteriorate microarchitecture of trabeculae in a time-dependent or an accumulative dose-dependent manner. Further, the remaining trabeculae appear to thicken in order to adapt to altered stress.

Bone health is vital through all life stages and has become a growing public health concern. The role of rhizoma drynariae (RD) as a traditional Chinese medicine for bone injury recovery has been widely investigated. Still, there is little research related to RD as a functional component in food to improve calcium bioavailability and bone health. Milk powder is a daily vital food source of dietary calcium. The present study aimed to investigate and compare the effects of a functional milk powder reinforced with RD extracts (RDE) or vitamin D, vitamin K2, and calcium, or both, using Sprague-Dawley rats, with both low calcium growing rat model and low calcium ovariectomized (OVX) rat model. For growing rats, RDE increased bone mineral density (BMD) and improved the microstructure of bone trabecula in the femur and lumbar vertebrae. The levels of serum bone turnover markers C-telopeptide of type Ⅰ collagen (CTX-I), procollagen type Ⅰ amino-terminal peptide (PINP), and osteocalcin (BGP) were increased with RDE supplementation. The tartrate-resistant acid phosphatase staining suggested a decrease in the number of osteoclasts in the femur. Immunohistochemistry showed that the osteoclast-related protein RANKL was downregulated, and the osteogenic-associated proteins RUNX2 and OSX significantly increased in the lumbar vertebrae. Similarly, in OVX rats, RDE improved BMD and microstructure in lumbar vertebrae, and the levels of CTX-I, PINP, and BGP were also increased. In conclusion, the novel functional milk powder supplemented with RDE facilitated osteogenesis and inhibited osteoclast in rats at both stages, especially with lumbar vertebrae in growing rats. Our findings provide new prospects and a more precise target for enhancing bone health by incorporating RDE as a functional component in milk powder.

Preparative expression and purification of a nacreous protein N16 and testing its effect on osteoporosis rat model

This systematic review and meta-analysis aimed to evaluate the correlations between the bone turnover markers (BTMs) and the bone mineral density (BMD) in patients treated for primary osteoporosis and to identify promising BTMs for the prediction of future BMD changes. The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for relevant studies that investigated the relationship between the BTMs and the BMD changes in patients treated for osteoporosis. All significant correlation coefficients of the baseline BTMs or changes in BTMs from baseline with the BMD changes from baseline under different interventions from eligible studies were used for systematic review and the subgroup analyses. The correlations were analyzed in terms of bone sites, intervention, time duration of BTMs measurements, and time duration of BMD measurements. Twenty-two records reporting correlation coefficients and the corresponding p-values were included, 13 of which were enrolled in the further subgroup analyses. The combined results from the systematic review and meta-analyses indicated that the changes in osteocalcin (OC), procollagen type I N propeptide (PINP), and urine N-terminal crosslinking telopeptide of type I collagen (U-NTX), or the PINP at baseline tended to be useful in evaluating the long-term BMD changes after drug intervention.

Bone mass is dramatically compromised during periods of weightlessness, inactivity, or bed rest. Animals that hibernate reduce their body temperature, heart rate and metabolic activity, and likewise lower bone turnover activity during their immobile state. Black bears Ursus americanus, however, do not hibernate, but rather overwinter by denning during which they maintain a nearly normal functional heart rate, cardiac output and temperature. Furthermore, markers of bone turnover in black bears are maintained during denning periods. Thus, the purpose of this work was to determine if the denning state of relative immobility in black bears results in changes in bone mass and bone architectural structure. Harvested forelimbs (ulna and radius) were compared between pre‐ and post‐denning black bears using X‐ray imaging, dual energy X‐ray absorptiometry, and micro‐computed tomography to quantify total distal forelimb bone mineral density, cancellous bone mineral density, bone mineral content, bone volume fraction, degree of anisotropy, structure model index, and trabecular thickness. No significant differences in any of the measured parameters were found in comparing radius and ulna from autumn and spring bears in this cross‐sectional sample, suggesting that black bears did not experience a significant change in bone mass or architecture during denning. The statistical power for detecting a significant difference (P≤ 0.05) for this sample was 0.8. The specific mechanism by which the preservation of bone was attained may be related to skeletal muscle interaction or circulating systemic hormones.

This study was performed to evaluate cortical bone strength in dogs using a quantitative ultrasound measurement device. In this study, 16 clinically healthy dogs with no lameness underwent measurement of the ultrasound propagation velocity of cortical bone (namely, speed of sound [SOS]) at the radius and tibia. Additionally, computed tomography examination with a calibration phantom was performed in 10 dogs. We calculated the bone mineral density (BMD) and Young's modulus from the computed tomography data using bone strength evaluation software. SOS, BMD, and Young's modulus were statistically compared between the radius and tibia. In addition, we examined the correlation between SOS and BMD and between SOS and Young's modulus. We also examined the correlation between SOS and age in the 13 dogs whose age was known. BMD and Young's modulus were not significantly different between the radius and tibia, but SOS was significantly different (P<0.05). Moreover, SOS and BMD showed a positive correlation in both radius and tibia. Similarly, SOS and Young's modulus showed a positive correlation. In addition, SOS and age showed a strong positive correlation (radius: r=0.77, P<0.05, tibia: r=0.83, P<0.05). Our finding that SOS of the radius and tibia cortical bone was correlated with BMD and Young's modulus indicates that quantitative ultrasound can be useful for evaluating cortical bone strength in dogs.

To investigate the Dynamic effects of glucocorticoid (GC) on bone mineral density and microarchitecture time-related changes of trabecular bone in bone mineral density (BMD) and microarchitecture in glucocorticoid-treated rats. Fifty-two 3.5-month-old female SD rats were randomly divided into 3 groups. Ten rats were killed at the beginning of experiment with their right tibiae taken out as the baseline group; 22 rats underwent subcutaneous injection of methylprednisolone once daily (GC-treated group), and the other 20 rats underwent subcutaneous injection of normal saline once daily as control group. One and 9 weeks after the beginning of experiment 11 and 10 rats from GCT Group and control group each were killed with their right tibiae taken out. High resolution micro-CT was used to identify the densitometric and microarchitectural properties of the trabecula in the proximal metaphysic of tibia. Compared with the control group the values of volumetric BMD (vBMD), tissue BMD (tBMD), bone volume fraction (BVF), trabecular number (Tb.N), degree of anisotropy (DA), and trabecular connectivity (Conn.D) in the trabecular bone at different time-points, of the GCT group all decreased; and the values in the ninth week were the lowest (all P < 0.05). The values of trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and structure model index (SMI) at different time-points of the GCT group were higher than those of the control group. A time-related analysis within the GCT group showed there was a declination in BVF, Conn.D, Tb.N, and DA with administration time, but Tb.Th and Tb.Sp were increased significantly (all P < 0.05). The mean values of Tb.Th in the first week and the ninth week of GCT Group were (0.076 +/- 0.020) mm and (0.086 +/- 0.026) mm respectively, both higher than the baseline value [(0.067 +/- 0.014) mm] and the values of the control group in the first and ninth weeks [(0.075 +/- 0.022) mm and (0.072 +/- 0.009) mm respectively]. Administration of GC time dependently decreases the BMD and causes deterioration in microarchitecture of trabecular bone; and the remaining trabeculae seem thicken to increase their strength as compensation.

The significance of high bone density in children

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide and it is associated with an increased risk of osteoporosis and fragility fractures. Our aim is to analyze the effect of T2DM on bone quality. This is a case-control study. The studied population consisted of 140 patients: 54 subjects with hip fracture (OP) without T2DM, 36 patients with hip fracture and T2DM (OP-T2DM), 28 patients with osteoarthritis (OA) without T2DM, and 22 patients with OA and T2DM (OA-T2DM). Bone markers, bone mineral density, FRAX score, microstructural, and bone material strength from femoral heads were assessed. The group with hip fracture presented lower BMD values than OA (p < 0.05). The OP, OP-T2DM, and OA-T2DM groups showed a decrease in bone volume fraction (BV/TV), in trabecular number (Tb.N), and in trabecular thickness (Tb.Th), while an increase was presented in the structural model index (SMI) and trabecular bone pattern factor (Tb.Pf), The groups OP, OP-T2DM, and OA-T2DM also presented lower values than those in group OA regarding the biomechanical parameters in the form of Young’s modulus or elastic modulus, toughness, ultimate stress, ultimate load, extrinsic stiffness, and work to failure (p < 0.05). Our results show the negative effect of type 2 diabetes mellitus on trabecular bone structure and mechanical properties.

BackgroundThis study is aimed to determine the efficacy of X-Ray Microtomography (micro-CT) in predicting oxytocin (OT) treatment response in rabbit osteoporosis(OP) model.MethodsSixty-five rabbits were randomly divided into three groups: control group, ovariectomy (OVX) -vehicle and OVX-oxytocin group. The controls underwent sham surgery. OVX-vehicle and OVX-oxytocin groups were subjected to bilateral OVX. The rabbits in OVX-oxytocin group were injected with oxytocin. In the 0th, 4th, 8th, 10th and 12th weeks post OVX operation, bone mineral density (BMD) and bone micro-architectural parameters were measured in three groups.ResultsBone mineral density (BMD), bone volume fraction (BV/TV), Trabecular Number (Tb.N), and Trabecular Thickness (Tb.Th) decreased, while Trabecular Spacing (Tb.Sp) and Structure Model Index (SMI) increased overtime in all the three groups. In OVX-oxytocin group, the bone deterioration tendency is slowing down compared with that of the OVX-vehicle group. The BMD of the OVX-oxytocin group was significantly lower than those in the OVX-vehicle group at 12th week (P = 0.017). BV/TV and Tb.Sp in OVX-oxytocin group changed significantly from 8th week (P = 0.043) and 12th week (P = 0.014), which is earlier than that of BMD and other bone micro-architectural parameters.ConclusionBV/TV and Tb.Sp changed prior to BMD and other bone micro-architectural parameters with oxytocin intervention, which indicate that they are more sensitive markers for predicting early osteoporosis and treatment monitoring when using micro-CT to evaluate osteoporosis rabbit model.

ObjectiveThe aim of the present study was to assess mineralization and trabecular microarchitecture in atrophic edentulous mandibles and to identify regional differences and relations with the extent of resorption. MethodsCortical and trabecular bone volumes in anterior, premolar and molar regions of 10 edentulous cadaveric mandibles (5 males and 5 females; mean age ± SD: 85.4 ± 8.3 years) were assessed by microcomputed tomography. Mandibular height and Cawood & Howell classes were recorded. Concerning trabecular volumes, bone mineral density (BMD), bone volume fraction, trabecular tissue volume fraction, connectivity density, trabecular number, trabecular thickness, trabecular separation, degree of anisotropy, and structural model index were measured; concerning cortical volumes porosity, BMD and cortical thickness were measured. ResultsIn molar regions, the bone volume fraction and trabecular number were lower, whereas trabecular separation, degree of anisotropy and cortical BMD were higher compared to anterior regions. In premolar regions, mandibular height correlated negatively with trabecular number (Spearman’s correlation r = 0.73, p = 0.017) and connectivity density (Spearman’s correlation r = 0.82, p = 0.004), and correlated positively with trabecular separation (Spearman’s correlation r = − 0.65, p = 0.04). Cortical BMD was higher at bucco-inferior cortex of molar and inferior border of premolar region and lower at anterior cranial buccal and lingual surface. ConclusionsIn the premolar region, increased resorption coincides with local impairment of trabecular bone quality. Cortical bone BMD is higher in areas with highest strains and lower in areas with most mandibular resorption. Trabecular bone volume and quality is superior in the anterior region of the edentulous mandible, which might explain improved primary stability of dental implants in this region.

Background and Aims Chronic kidney disease (CKD) is a crucial risk factor for biochemical and bone disturbances, as well as non-skeletal calcifications known as Chronic Kidney Disease – Mineral and Bone Disorders (CKD-MBD). Etiopathogenesis of CKD-MBD still remains unknown and arouses much controversy. Indoxyl sulfate (IS) is one of the most potent protein-bound uremic toxin that accumulates during CKD, and exerts aggressive and multidirectional effect on the body. In vitro studies indicate that IS modulates the differentiation and activation of osteoblasts and osteoclasts, however IS impact on bone and mineral disorders still remains unclear. The purpose of the study was to assess IS effect on bone turnover markers, parathyroid hormone (PTH), vitamin D3, and densitometric and biomechanical properties of bones in rat model. Method Male Wistar rats weighting 180 – 210 g (n=48) were divided into three groups – control group that received pure water and two experimental groups. Experimental groups were exposed to IS in the doses of 100 or 200 mg/kg of b.w. (200 IS) in the drinking water during 4 weeks. At the end of experiment, rats were anesthetized and samples of blood, as well as tibiae, femurs and lumbar spines were collected. Next, the IS bone (cortical and trabecular), plasma and urine levels were determined by high-performance liquid chromatography (HPLC). We also assessed IS influence on bone turnover markers (alkaline phosphatase – ALP, and tartrate-resistant acid phosphatase - TRAP), and level of vitamin D3, and PTH. Furthermore, we evaluated densitometric parameters of tibiae, femurs and lumbar spines using Horizon QDR Series X-ray Bone Densitometer, and performed biomechanical parameters analysis of the cortical bone of the femoral diaphysis using three-point bending test, and the mixed cortico-trabecular structure of the proximal femur by the bending test of the femoral neck. Results Chronic exposure to IS led to statistically significant increase in plasma, urine, cortical and trabecular bone IS concentrations. We observed reduction in bone turnover markers – bone formation marker ALP in trabecular and cortical bone, and bone resorption marker TRAP in cortical bone. Moreover, the highest dose of IS increased PTH. None of tested IS doses affected vitamin D3. From data obtained due to biomechanical tests, the highest dose of IS decreased the main indicators of bone strength: yield load (Fy) and displacement at yield [dl(Fy)] of femoral diaphysis and femoral neck, and ultimate load (Fu) and displacement at ultimate [dl(Fu)] of femoral diaphysis. Furthermore, we observed the decrease in elasticity of femoral diaphysis (increased Young’s modulus of elasticity E). Additionally, densitometric measurements revealed reduction only in the bone mineral density (BMD) and BMD of diaphyseal area (BMD R2) of tibiae, BMD R2 of femurs in 200 IS group, as well as BMD and BMD R2 of tibiae in 100 IS group. Conclusion Obtained data confirm that IS affects bones. We observed reduced bone metabolism and strength after exposure to IS. On the basis of the results, we concluded that IS can be one of crucial uremic factors responsible for increased risk of fracture during CKD.

Background Osteoporosis is a common bone disease characterized by reduced bone mass resulting from continuous bone resorption. Methods PubMed, Scopus, and Embase were searched to find published trials on the effect of soy isoflavones on bone mineral density (BMD) and bone turnover markers (bone-specific alkaline phosphatase, osteocalcin, osteoprotegerin, pyridinoline, deoxypyridinoline, C-telopeptide, and N-telopeptide). Random-effects inverse-variance model was used to calculate the pooled effects. Results A total of 5313 articles were found, screened, and assessed for eligibility, and finally 52 trials were included in the meta-analysis. Consumption of soy isoflavones caused significant improvement in BMD of lumbar spine (mean difference (MD) = 0.76%; 95% CI: 0.09, 1.42%; p = 0.03), hip (MD = 0.22%; 95% CI: 0.02, 0.42%; p = 0.04), and femoral neck (MD = 2.27%; 95% CI: 1.22, 3.31%; p < 0.001). Subgroup analysis showed that in all 3 sites, the improvement was significant in normal weight subjects and interventions longer than a year, although trial location and dosage were also factors influencing isoflavones’ impact on BMD. Among markers of bone turnover, osteoprotegerin (MD = 5.79; 95% CI: 3.08, 8.51 pg/ml; p < 0.001), pyridinoline (MD = −5.13; 95% CI: −7.76, −2.50 nmol/mmol; p < 0.001), and C-telopeptides (MD = −0.08; 95% CI: −0.16, −0.00 ng/ml; p = 0.04) were favorably affected by isoflavones while osteocalcin and bone alkaline phosphatase did not change. Subgroup analysis of bone markers showed that in overweight/obese individuals and dosages <90 mg/day, isoflavones are more effective. Conclusions Soy isoflavones prevent osteoporosis-related bone loss in any weight status or treatment duration. They increase BMD in normal weight subjects and diminish bone resorption in overweight/obese individuals. Although bone resorption may be decelerated over short-term isoflavone consumption, periods longer than a year are probably needed to affect BMD. Isoflavones also appear benefits on bone in any dose or subjects’ ethnicity.

Surrogates for fracture endpoints in clinical trials.