Denosumab Improves Glomerular Filtration Rate in Osteoporotic Patients With Normal Kidney Function by Lowering Serum Phosphorus.

Higher serum phosphorus (Pi) increases the risk for chronic kidney disease (CKD). It was reported that a single administration of denosumab or zoledronate significantly suppressed serum Pi levels as well as those of bone resorption markers in serum. Also, previous evidences suggest a link between bone anti-resorptive therapy and vasoprotective/renoprotective effects through mechanisms that remain unexplored. The aim of this study is to assess the renoprotective effect of denosumab and involvement of denosumab-induced reduction in serum Pi in osteoporotic patients. Osteoporotic patients (n = 73) without overt proteinuria in dipstick test results were treated with denosumab (60 mg) every 6 months during the study period (24 months). Estimated glomerular filtration rate based on serum cystatin C (eGFRcys) was used as a filtration marker and tartrate-resistant acid phosphatase-5b (TRACP-5b) as a bone resorption marker. For analysis of non-CKD patients (n = 56), those with eGFRcys <60 mL/min/1.73 m2 were excluded. A single injection of denosumab suppressed serum Pi as well as TRACP-5b during the first 6 months, whereas age-related decline in eGFRcys was significantly reversed, with an increase of 2.75 ± 1.2 mL/min/1.73 m2 after 24 months noted. Multivariate analysis showed that serum Pi reduction following the initial denosumab injection was positively associated with serum TRACP-5b suppression during that same period (ß = 0.241, p = 0.049). In addition, a positive association of serum Pi suppression, but not of corrected calcium or TRACP-5b, with eGFRcys increase after 24 months (ß = 0.321, p = 0.014) was found after adjustments for gender, age, BMI, antihypertensive drug use, albumin, and eGFRcys. The same was observed in osteoporotic cases restricted to non-CKD patients. In conclusion, serum Pi reduction resulting from phosphorus load decrement from bone induced by denosumab is a determinant for eGFRcys increase. Early introduction of bone antiresorptive therapy can retain glomerular filtration in osteoporosis cases, including non-CKD patients. © 2019 American Society for Bone and Mineral Research.

Eldecalcitol increases bone mineral density in Chinese osteoporotic patients without vitamin D or calcium supplementation.

Eldecalcitol increased bone mineral density (BMD) and prevented vertebral fractures in vitamin D-sufficient osteoporotic subjects. However, the effect of eldecalcitol on BMD under vitamin D insufficiency is unknown. We examined the effect of eldecalcitol on BMD compared with alfacalcidol in osteoporotic patients without vitamin D or calcium supplementation. This is a randomized, double-blind, active comparator trial. 265 Chinese osteoporotic patients were randomly assigned to receive 0.75 µg eldecalcitol or 1.0 µg alfacalcidol for 12 months without vitamin D or calcium supplementation. Baseline calcium intakes were less than 550 mg/day and mean serum 25-hydroxyvitamin D [25(OH)D] was below 43 nmol/L in both groups. Baseline BMD tended to be lower in patients with lower calcium intake and serum 25(OH)D. Lumbar BMD increased by 2.05% higher in eldecalcitol than alfacalcidol group at 12 months. Total hip and femoral neck BMD also increased by 1.33 and 1.78%, respectively, in the eldecalcitol than the alfacalcidol group. The effect of eldecalcitol on BMD was not affected by serum 25(OH)D or calcium intake. The incidence of adverse events was not different between the two groups. Incidence of hypercalcemia in the edecalcitol group was not affected by serum 25(OH)D. In conclusion, baseline BMD tended to be lower in patients with low calcium intake and serum 25(OH)D. Eldecalcitol increased lumbar and hip BMD more than alfacalcidol regardless of serum 25(OH)D or calcium intake without vitamin D or calcium supplementation. These results suggest that eldecalcitol is effective in increasing the BMD of osteoporotic patients regardless of vitamin D status or calcium intake.Clinical Trial Registration number JAPIC CTI 152904.

The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis.

As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone-sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C-cells. Fifteen-month-old Wistar rats were either bilaterally orchidectomized (Orx) or sham-operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg-1 b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C-cells by immunohistochemical staining for thyroglobulin and CT. Thyroid follicular epithelium, interstitium, colloid and CT-immunopositive C-cells were examined morphometrically. Serum concentrations of osteocalcin (OC), triiodothyronine (T3 ), thyroxine (T4 ) and CT were determined as well as urinary calcium (Ca2+ ) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P < 0.05), but trabecular separation (Tb.Sp) was decreased (P < 0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P < 0.05) compared with Orx, whereas Vv of the colloid was lower (P < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC, T3 , T4 and urinary Ca2+ concentrations (P < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.

An intergated serum and urinary metabonomic research based on UPLC-MS and therapeutic effects of Gushudan on prednisolone-induced osteoporosis rats.

Gushudan, a Chinese compound formulation based on the theory of traditional Chinese medicine and desgined to treat osteoporosis. However, its intergated intervention effective mechanism in vivo is not well understood. In this study, an intergated serum and urinary metabonomic strategy based on UPLC-MS technique have been developed to increase the understanding of the metabolism characters of osteoporosis and to investigate the holistic therapeutic efficacy of Gushudan on prednisolone-induced osteoporosis rat model. Principle component analysis (PCA) was utilized to identify differences in metabolic profiles of rats in the control group, prednisolone-induced osteoporosis model group and Gushudan-treatment group and clear separation was achieved among three groups. Furthermore, 17 potential biomarkers from urine and 10 potential biomarkers from serum were identified, primiarily related to amino acid metabolism, energy metabolism, lipid metabolism, intestinal flora metabolism and kidney damage. Gushudan has therapeutic effects on rat with osteoporosis via the regulation of multiple metabolic pathways. It's worth mentioning that some new biomarkers associated with osteoporosis such as 3-methoxydopa, 2,8-digydroxyadenine have been discovered in this study for the first time. This study provides a useful approach to get insight into the intergated metabonomic mechanism of prednisolone-induced osteoporosis and to assess the efficacy of Gushudan on osteoporotic rats. The work also shows that the metabonomics method is a promising tool in the efficacy and mechanism research of traditional Chinese compound medicines.

Comparison of clinical cut-points and treatment targets for urine NTX and plasma ßCTX-I in osteoporosis.

OBJECTIVE: We undertook to identify levels for plasma ß isomerised carboxy-terminal telopeptides of type I collagen (p-ßCTX-I) that are comparable to currently used urine amino-terminal telopeptides of type I collagen (u-NTX) cut-points and treatment targets in osteoporosis. DESIGN AND METHODS: Fasting morning samples were collected from patients attending tertiary hospitals and clinics for investigation of metabolic bone disease. Patients with Paget's disease or <20years of age were excluded. Second void spot urine for NTX and plasma (EDTA) samples were utilised. Urine was analysed routinely and plasma stored at -20C until analysis by enzyme-linked immunosorbent assay (ELISA) (Immunodiagnostic Systems plc), E170 (Roche Diagnostics) and IDS-iSYS (Immunodiagnostic Systems plc) methods. The relationship of u-NTX with each p-ßCTX-I method's results was assessed by Passing and Bablok regression, and p-ßCTX-I levels equivalent to u-NTX cut-points and targets were interpolated. RESULTS: One hundred and forty six patients were included. Spearman correlation coefficients ranged from 0.71 to 0.75 for the three ßCTX-I assays. The equivalent ßCTX-I concentrations for NTX/Cr values of 21 (fracture risk reduction target following risedronate therapy), 27 (healthy pre-menopausal women's mean value), and 38 (threshold for reduction of BMD on calcium alone) nmol BCE/mmol were 230, 312 and 462ng/L for the automated Roche assay and 271, 395 and 624ng/L for the automated IDS i-SYS assay respectively. CONCLUSIONS: The p-ßCTX-I equivalent to the only available fracture outcome based absolute treatment threshold of 21nmol BCE/mmol established for u-NTX, is close to 250ng/L but will vary between p-ßCTX-I assays.

Osteoprotective Effect of Echinocystic Acid, a Triterpone Component from Eclipta prostrata, in Ovariectomy-Induced Osteoporotic Rats.

Echinocystic acid (EA) is a natural triterpone enriched in various herbs and has been used for medicinal purposes in China. In the present study, we systematically examined the effects of EA on ovariectomy-induced osteoporosis in rats for the first time. Three-month-old female ovariectomy (OVX) Sprague-Dawley rats were used to evaluate the osteoprotective effect of EA. Results showed that administration of EA (5 or 15 mg/kg/day) for 12 weeks prevented lower levels of maximum stress and Young's modulus of femur induced by OVX. EA also recovered bone metabolic biomarkers levels in OVX rats, including osteocalcin, alkaline phosphatese, deoxypyridinoline, and urinary calcium and phosphorus. EA (5 and 15 mg/kg/day) could prevent the alteration of total bone mineral density in the femur caused by OVX. However, only high dose (15 mg/kg/day) of EA significantly improved trabecular architecture, as evidenced by higher levels of bone volume/tissue volume, trabecula number, and trabecula thickness, and lower levels of trabecula separation and structure model index compared with OVX rats. In addition, EA treatment decresed the serum levels of IL-1ß and TNF-α in OVX rats. In conclusion, EA could prevent reduction of bone mass and strength and improve the cancellous bone structure and biochemical properties in OVX rats. Hence, EA may serve as a new candidate or a leading compound for anti-osteoporosis.

The importance of calciuria as lithogenic factors in patients with osteopenia/osteoporosis.

PURPOSE: Recurrent kidney stones are associated with bone mineral density loss, altered bone remodeling markers, hypercalciuria and increased in fasting calcium/creatinine ratio. The objective was to determine biochemical alterations in urine in patients with osteopenia/osteoporosis without calcium kidney stones compared with patients with calcium kidney stones. METHODS: This is a cross-sectional study including 142 patients who were divided in two groups: Group 1 (patients with recurrent calcium kidney stones) and Group 2 (patients with osteopenia/osteoporosis in the lumbar spine or hip). Analyses of bone mineral density, calcium-phosphorous and bone metabolism and lithogenic risk factors in fasting urine samples and 24-h urine samples were performed. Statistical analysis was carried out with SPSS 17.0. A p ≤ 0.05 was considered statistically significant. RESULTS: Patients in Group 2 presented greater loss of bone mineral density and more elevated alkaline phosphatase, iPTH, phosphorous and ß-crosslaps levels, as compared to patients in Group 1. However, Group 1 presented greater urine calcium, oxalate and uric acid and a higher proportion of hypocitraturia, hypercalciuria and hyperoxaluria, as compared to Group 2. Multivariate analysis revealed that advanced age and ß-crosslaps levels are risk factors for bone mineral density loss, while low urinary calcium excretion was protective against bone demineralization. CONCLUSION: Patients with osteopenia/osteoporosis without lithiasis present some urinary biochemical alterations. This would explain the lack of lithogenic activity, although low calcium excretion in 24-h urine samples is a protective factor against the loss of bone mineral density.

Prevention of osteoporosis by oral administration of phytate-removed and deamidated soybean ß-conglycinin.

Phytate-removed and deamidated soybean ß-conglycinin (PrDS) prepared by ion-exchange resins was supplemented to be 4% in the diet administered to ovariectomized rats to investigate its preventive effect on osteoporosis. The apparent calcium absorption rate decreased following ovariectomy and was not replenished by oral administration of phytate-removed soybean ß-conglycinin (PrS) or casein. On the other hand, administration of PrDS restored the calcium absorption rate to the same level as the sham group. Markers of bone resorption, such as serum parathyroid hormone (PTH) and urinary deoxypyridinoline (DPD), increased, and the bone mineral density and breaking stress decreased following ovariectomy. However, PrDS supplementation suppressed the changes caused by the decrease in calcium absorption from the small intestine. Therefore, PrDS supplementation shows promise for the prevention of postmenopausal osteoporosis.

Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats.

CONTEXT: Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats. OBJECTIVE: This study investigates the effect of RDE against bone loss induced by simulated microgravity. MATERIALS AND METHODS: A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague-Dawley rats were divided into four groups (n = 6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0 mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500 mg/kg/d). RDE or ALN was administrated orally for 4 weeks. RESULTS: Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index. DISCUSSION AND CONCLUSION: RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.

Safety and efficacy of polycalcium for improving biomarkers of bone metabolism: a 4-week open-label clinical study.

Polycalcium is a mixture of Polycan and calcium lactate-gluconate 1:9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies. These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety. In total, 30 healthy women (range 40-60 years) were administered 400 mg of Polycalcium for 4 weeks. The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium. After 4 weeks of Polycalcium administration, 27 subjects completed the test plan. Three subjects withdrew their consent to participate. The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by -28.44%, 14.37%, 6.11%, and 1.42%, respectively. Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by -13.40%, 6.67%, -5.13%, -22.43%, and -3.04%, respectively. Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400 mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe. Polycalcium was apparently safe and efficacious.

Comparative activities of the S-enantiomer and racemic forms of equol on bone fragility in ovariectomized mice.

We compared the effects of the S-enantiomer and racemic forms of equol on bone using ovariectomized (OVX) mice. Femoral bone mineral density and bone strength decreased in the OVX mice, but not in OVX mice administered 0.5 mg/d S-equol. This, however, did not hold for racemic equol. Serum and urine S-equol concentrations were higher in the mice administered S-equol than in those administered racemic equol. These results suggest that the inhibitory effects of S-equol on bone fragility in OVX mice are greater than those of racemic equol.

[Metabonomic study on protective effect of ethanol extracts of drynariae rhizoma on osteoporosis in rats urine by using UPLC-MS/MS].

This paper was designed to study metabonomic characters of the osteoporosis induced by high dose of hydrocortisone and the protective effects of Drynariae Rhizoma, which can replenish the kidney and strengthen the bones. A urinary metabonomics method based on ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) was developed. Clear separation of healthy control group, model group and treatment group was achieved by using the principal components analysis (PCA) and 9 significantly changed metabolites were identified as potential biomarkers of osteoporosis. Compared with the health control group, the model group rats showed lower levels of creatinine, citric acid, azelaic acid, hippurate, tryptophan and indoxyl sulfate together with higher levels of phenylalanine, cresol sulfate and phenaceturic acid. These changes in urinary metabolites suggest that the disorders of amino acid metabolism, energy metabolism, gut microflora and anti-oxidative damage are related to osteoporosis induced by high dose of hydrocortisone and the potential effect of Drynariae Rhizoma on all the four metabolic pathways.

Achyranthes bidentata root extract prevent OVX-induced osteoporosis in rats.

AIM: The objective of the present study was to systematically investigate the effects of Achyranthes bidentata root extract (ABRE) on postmenopausal osteoporosis. MATERIALS AND METHODS: Eighty 3-month-old female Sprague-Dawley rats were used and randomly assigned into sham-operated group (SHAM) and five ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX); OVX with 17 ß-ethinylestradiol (E(2), 25 µg/kg/day); OVX with ABRE of graded doses (100, 300, or 500 mg/kg/day). Daily oral administration of ABRE or E(2) started on week 4 after OVX for 16 weeks. Bone mass, bone turnover and strength were analyzed by dual-energy X-ray absorptiometry (DEXA), biochemical markers and three-point bending test. The trabecular bone microarchitecture was evaluated by microcomputed tomography (µCT). RESULTS: 16 weeks treatment of ABRE slowed down the body weight gain and prevented the loss of bone mass induced by the OVX. The prevention effect on bone loss was due to altering the rate of bone remodeling, which could be inferred from the decreased level of bone turnover markers, such as serum alkaline phosphatase (ALP), osteocalcin (OC) and urinary deoxypyridinoline (DPD). The changes of urinary calcium and phosphorus excretion provided the same evidence. The treatment could also enhance the bone strength and prevent the deterioration of trabecular microarchitecture. CONCLUSIONS: We conclude that 16 weeks of ABRE treatment improve bone biomechanical quality through modifications of bone mineral density (BMD), and trabecular microarchitecture without hyperplastic effect on uterus, and it might be a potential alternative medicine for treatment of postmenopausal osteoporosis.

Soy isoflavones for osteoporosis: an evidence-based approach.

Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.

Biochemical markers of bone turnover as predictors of osteoporosis and osteoporotic fractures in men and women: 10-year follow-up of the Taiji cohort.

We aimed to assess the capacity of biochemical markers of bone turnover (BTMs) to predict bone loss, osteoporosis (OP), and osteoporotic fractures. We randomly selected 400 individuals (age 40-79 years in 1993; 50 of each gender and age stratum) from a list of registered residents. In the years 1993, 1996, 2000, and 2003, bone mineral density (BMD) of the spine and hip were measured by dual-energy X-ray absorptiometry. The BTMs assessed at baseline were serum intact osteocalcin (OC), total OC, bone-specific alkaline phosphatase, C-terminal propeptide of type I procollagen, N-terminal propeptide of type I procollagen (PINP), C-terminal cross-linking telopeptide of type I collagen generated by matrix metalloproteinase, C-terminal cross-linking telopeptide of type I collagen (beta-CTX), N-terminal cross-linking telopeptide of type I collagen (NTX), urinary pyridinoline, and deoxypyridinoline (DPD). For 307 completers, multivariate analysis after adjusting for confounders revealed that serum PINP levels in men [hazard ratio (HR) 2.80, P < 0.05] and serum PINP (HR 1.65, P < 0.05), beta-CTX (HR 1.80, P < 0.001), NTX (HR 1.96, P < 0.01), and urinary DPD levels (HR 1.40, P < 0.05) in women were significantly related to the occurrence of spinal OP. In addition to adjustment for the baseline status of BMD, i.e., osteopenia or normal range, PINP, beta-CTX, and NTX in women could significantly predict the future occurrence of spinal OP. BTMs were not significant predictors of bone loss, femoral OP, or osteoporotic fractures. In conclusion, various BTMs in women can predict the occurrence of spinal OP.

Total flavonoid fraction of the Herba epimedii extract suppresses urinary calcium excretion and improves bone properties in ovariectomised mice.

Flavonoids are the active components of Herba epimedii (HEP), a commonly used herb for the management of osteoporosis in China over the centuries. The present study aims to characterise the in vivo effects of its total flavonoid (TF) fraction on bone properties and mineral metabolism as well as to study the mechanism involved in achieving its protective effects against ovariectomy (OVX)-induced bone loss. TF suppressed OVX-induced increase in urinary Ca excretion as well as loss of bone mass and strength at the distal femur in mice in a dose-dependent manner. The changes in urinary Ca excretion were inversely correlated with the expressions of renal Ca transport protein (CaBP-28K) and vitamin D receptor mRNA in OVX mice. TF (100 µg/g) treatment prevented the deterioration of trabecular bone microarchitecture induced by OVX in mice. In addition, TF treatment increased the expression of type I collagen and osteocalcin mRNA and the ratio of osteoprotegerin/receptor activator of NF-κB ligand mRNA, and suppressed the increase in IL-6 mRNA induced by OVX in the femur of mice. The present results indicate that the optimal dosage of the TF fraction of HEP for the improvement of bone properties and mineral metabolism in OVX mice was between 50 and 100 µg/g. Mechanistic studies indicated that TF might increase renal Ca reabsorption, stimulate the process of osteoblast formation as well as suppress the process of osteoclastogenesis in OVX mice.

Effect of soybeans and sword beans on bone metabolism in a rat model of osteoporosis.

BACKGROUND/AIMS: Soy isoflavones have been reported to prevent bone loss in rat models of osteoporosis. However, the effect of the natural soybeans that people consume in their diet needs to be explored. In the present study, we evaluated the effects of yellow and black soybeans (Glycine max), and sword beans (Canavalia gladiate) on bone mineral density (BMD), bone mineral content (BMC), and bone biomarkers in ovariectomized (OVX) rats. METHODS: Seven-week-old female Sprague-Dawley rats were raised for 2 weeks on a calcium-free diet based on the American Institute of Nutrition (AIN)-93M diets. All the rats received OVX, were randomized to one of four groups, and given one of the diets supplemented with casein, yellow soybean, black soybean, and sword bean for 10 weeks. BMD, BMC, osteocalcin (OC; a bone formation biomarker), deoxypyridinoline (DPD; a bone resorption biomarker), and TNF-alpha (a bone resorption cytokine) were assessed. RESULTS: In the femur and lumbar spine, BMD and BMC were significantly higher in the various bean groups than in the casein group. Among the bean groups, femur and spine BMD were significantly higher in the yellow soybean and sword bean groups than in the black soybean group. Femur BMC was the highest in the yellow soybean group, and spine BMC was not significantly different between the various bean groups. Plasma OC concentrations and urinary DPD excretion were significantly higher in the casein group than in the various bean groups. The sword bean group showed significantly lower OC and DPD levels than the yellow and black soybean groups. There were no significant differences between the yellow and black soybean groups. TNF-alpha concentrations were not significantly different between the four groups. CONCLUSION: Consumption of yellow and black soybeans, and sword beans had a definite protective effect on bone loss in OVX rats by inhibiting bone turnover and preventing bone resorption. Furthermore, consumption of sword beans may help prevent postmenopausal osteoporosis.

Circadian rhythm affects the preventive role of pulsed electromagnetic fields on ovariectomy-induced osteoporosis in rats.

Pulsed electromagnetic fields (PEMF) have been proved effective in the prevention of osteoporosis both experimentally and clinically. Chronotherapy studies have shown that circadian rhythm (CR) played an important role in the occurrence, development and treatment of several diseases. CR has also been recognized as an essential feature of bone metabolism. Therefore, it is of therapeutic significance to investigate the impact of CR on the efficacy of PEMF in the prevention of osteoporosis. However, this issue has never been discussed previously. The objective of this study was to systematically evaluate the impact of CR on the preventive effect of PEMF on osteoporosis in rats. Thirty-two 3 month old female Sprague-Dawley rats were randomly divided into four different groups: sham-operated control (Sham), ovariectomy (OVX), OVX with PEMF stimulation in daytime (OVX+DPEMF) and OVX with PEMF stimulation in nighttime (OVX+NPEMF) groups. The OVX+DPEMF and OVX+NPEMF groups were subjected to daily PEMF exposure on the 2nd post-operative day, from 9:00 to 15:00, and 0:00 to 6:00, respectively. After 12 weeks, the OVX+DPEMF group presented better efficacy in prevention against OVX-induced bone loss and deterioration of trabecular bone architecture compared with the OVX+NPEMF group. This was evidenced by the increased levels of femoral bone mineral density, trabecular area percentage, trabecular thickness, trabecular number and decreased trabecular separation. Furthermore, the bone turnover biomarkers (serum alkaline phosphatase, serum bone Gla protein and urinary deoxypyridinoline) and the dynamic histomorphometric parameters reflecting the trabecular osteoblast and osteoclast activity (bone formation rate with bone volume as referent, osteoclast number, etc.) in the OVX+DPEMF group decreased to a larger extent compared with the OVX+NPEMF group. In conclusion, the results indicated that CR was an important factor determining the preventive effect of PEMF on osteoporosis and PEMF exposure in the daytime presented better stimulus efficacy in rats. The findings might be helpful for the efficacious use of PEMF mediations, evaluation of PEMF action and experimental design in the future studies of biological effect of electromagnetic fields.

Phosphate decreases urine calcium and increases calcium balance: a meta-analysis of the osteoporosis acid-ash diet hypothesis.

BACKGROUND: The acid-ash hypothesis posits that increased excretion of "acidic" ions derived from the diet, such as phosphate, contributes to net acidic ion excretion, urine calcium excretion, demineralization of bone, and osteoporosis. The public is advised by various media to follow an alkaline diet to lower their acidic ion intakes. The objectives of this meta-analysis were to quantify the contribution of phosphate to bone loss in healthy adult subjects; specifically, a) to assess the effect of supplemental dietary phosphate on urine calcium, calcium balance, and markers of bone metabolism; and to assess whether these affects are altered by the b) level of calcium intake, c) the degree of protonation of the phosphate. METHODS: Literature was identified through computerized searches regarding phosphate with surrogate and/or direct markers of bone health, and was assessed for methodological quality. Multiple linear regression analyses, weighted for sample size, were used to combine the study results. Tests of interaction included stratification by calcium intake and degree of protonation of the phosphate supplement. RESULTS: Twelve studies including 30 intervention arms manipulated 269 subjects' phosphate intakes. Three studies reported net acid excretion. All of the meta-analyses demonstrated significant decreases in urine calcium excretion in response to phosphate supplements whether the calcium intake was high or low, regardless of the degree of protonation of the phosphate supplement. None of the meta-analyses revealed lower calcium balance in response to increased phosphate intakes, whether the calcium intake was high or low, or the composition of the phosphate supplement. CONCLUSION: All of the findings from this meta-analysis were contrary to the acid ash hypothesis. Higher phosphate intakes were associated with decreased urine calcium and increased calcium retention. This meta-analysis did not find evidence that phosphate intake contributes to demineralization of bone or to bone calcium excretion in the urine. Dietary advice that dairy products, meats, and grains are detrimental to bone health due to "acidic" phosphate content needs reassessment. There is no evidence that higher phosphate intakes are detrimental to bone health.

A case of magnesium deficiency associated with insufficient parathyroid hormone action and severe osteoporosis.

The relationship between osteoporosis and magnesium (Mg) deficiency is still controversial. Here we report a case of an 82-year-old woman with a giant adenomatous goiter and severe osteoporosis with multiple vertebral fractures, whose clinical course indicated that her osteoporosis was probably due to Mg deficiency. She visited our hospital for treatments of tetany. Laboratory data showed the existence of hypomagnesemia, hypocalcemia, hypokalemia, vitamin D deficiency, and slightly elevated intact PTH. Intravenous administration of Mg not only improved these electrolyte abnormalities but also increased serum levels of intact PTH, bone formation markers, 1,25-dihydroxyvitamin D, as well as bone resorption markers in the urine, and lowered urinary phosphate reabsorption. Hypomagnesemia on admission seemed to arise from long-lasting poor food intake and malnutrition, because it improved after the disappearance of dysphagia with a goiter resection. After the operation, BMD values at the lumbar spine and femoral neck obviously increased during 6 months of Mg supplementation without any specific therapies for osteoporosis. Mg deficiency in this case seemed to cause impaired secretion of PTH from the parathyroid and the refractoriness of bone and kidney to the hormone, which led to the suppression of both bone remodeling and renal vitamin D production. These processes were probably linked to her severe osteoporosis, which was reversed by Mg supplementation.