Animals ; Body Weight ; drug effects ; Bone Remodeling ; drug effects ; Growth and Development ; drug effects ; physiology ; Isoflavones ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood

This study was purposed to investigate the short-term effects of citrate administration on bone metabolism in the healthy blood donor volunteers. A crossover, placebo-controlled trial were conducted on 22 healthy blood donor volunteers. The volunteers received either a standardized infusion of citrate at 1.5 mg/(kg.min) or the equal volume of placebo normal saline, were washout for 2-3 weeks. During washout serial blood samples were collected and analyzed for bone biochemical markers and electrolytes, such as bone formation marker osteocalcin (OC), bone resorption marker carboxyterminal telopeptide of type I collagen (CTX), intact parathyroid hormone ((i)PTH), ionized calcium ((i)Ca(2+)) and phosphorus (P(i)). Serial urine samples were collected and analyzed for Ca(2+), P(i) and creatinine concentration. The results showed that compared with placebo group, infusion of citrate increased serum levels of OC and CTX (p < 0.0001). The greatest increase of OC and CTX levels occurred at the completion of the intervention. The increment of CTX was higher than OC (p = 0.02), and the OC/CTX ratio decreased (p < 0.01). Infusion of citrate also induced profound increase in serum (i)PTH level (p < 0.0001) and urinary calcium excretion (p < 0.0001), and decrease in serum (i)Ca(2+) (p < 0.0001) and P(i) (p < 0.01) levels. The decrease of (i)Ca(2+) level in female was higher than that in male (p = 0.007), but the changes of (i)PTH, OC, and CTX levels showed no differences between female and male. Changes of OC and CTX levels were closely related to each other (r = 0.56, p < 0.0001) and changes of both markers were negatively correlated with the change of serum (i)Ca(2+) concentration during the citrate intervention(r(OC) = -0.44, r(CTX) = -0.44, p < 0.0001). Increased levels of (i)PTH showed positively correlation with OC (r = 0.34, p = 0.02) and borderline correlation with CTX (r = 0.29, p = 0.06) in male. No such relationship was observed in female. All bone markers and electrolyte levels returned to baseline within 24 hours. It is concluded that the citrate load at the dose as a single platelet apheresis results in profound increase of bone turnover, which is characterized by a short-term increase of bone resorption and excretion of calcium. The possible effect of citrate on bone mass of long-term frequent platelet apheresis donor is worth concerning.
Adult ; Blood Donors ; Bone Remodeling ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Citric Acid ; pharmacology ; Cross-Over Studies ; Female ; Humans ; Male ; Osteocalcin ; blood

BACKGROUNDThe association of long-term bisphosphonate treatment for osteoporosis and related safety problems such as atypical fractures were not clearly defined. This study was to evaluate the structural, densitometric and biomechanical properties of the prolonged bisphosphonate-loaded bones.

METHODSBone mineral density (BMD) at hip and femoral midshaft, bone cross-sectional area, moment of inertia of both femurs, bone formation and resorption biochemical markers were compared between 28 elderly with at least 4 years of bisphosphonate treatment from 2002 through 2006 and age-matched group of 37 elderly.

RESULTSThe total hip BMD and t-score were found not different between two groups. However, bisphosphonate treated patients were found to have significantly lower bone mineral content in the femoral shaft (P < 0.05); morphological study showed lower cross-sectional area in subtrochanteric and mid-diaphyseal region and thus significantly lower moment of inertia (P < 0.01). High resolution-peripheral quantitative computed tomography showed significantly decreased trabecular density, bone volume ratio, trabecular number but increased trabecular spacing in tibia and distal radius. Finite element analysis further confirmed significantly lower stiffness and failure load in tibia. Biochemical studies also showed lower bone resorption and severely suppressed bone formation activity (P < 0.001).

CONCLUSIONSThe unchanged total hip BMD between two groups confirmed the beneficial effects of bisphosphonate on trabecular bone, thus preventing osteoporotic fractures at large in previous studies. However, the inferior structural, densitometric and biomechanical properties at cortical bones, especially femur midshaft, need a special attention to look into the association between long-term bisphosphonate intake and the occurrence of stress fractures. When patients taking bisphosphonate complain of proximal thigh pain or discomfort, plain X-ray film can be the first line screening. All patients prescribed with bisphosphonate should be informed of such a complication though we must stress its rarity.

Aged ; Aged, 80 and over ; Biomechanical Phenomena ; Bone Density ; drug effects ; Bone Density Conservation Agents ; adverse effects ; Bone Remodeling ; drug effects ; Densitometry ; Diphosphonates ; adverse effects ; Female ; Finite Element Analysis ; Humans ; Male ; Middle Aged ; RANK Ligand ; blood

This study was designed to investigate the effects of some Traditional Chinese Medicine (TCM) agents on bone resorption and morphometric features of osteoclasts as well as their relationships. TCM ShengGuZaiZaoSan and XianLingGuBao, were used to treat the experimental fracture. Thirty 6-month-old Chinchilla rabbits were used for the establishment of animal models each with a 3 mm bone defect in the middle of left radius as well as of right radius. These models were divided randomly into 3 groups : ShengGuZaiZaoSan Group (Group A), XianLingGuBao groups (Group B) and control-group (Group C). Every group was further divided into 2 subgroups: a former sacrificed group (14 days after operation) and a latter sacrificed group (31 days after operation). After the rabbits being killed, the samples of their undecalcified calli were subjected to the morphometry study of bone resorption and osteoclasts. Group A had more bone resorption, compared with Group B and C. Both Groups A and B exhibited some changed morphometric features of osteoclasts as compared with Group C (P < 0.05). Simple correlation analysis indicated that bone resorption is mainly correlated with osteoclast numbers, and that in individual group, bone resorption is correlated with osteoclast form factor, area and mean photodensity (P < 0.05). These allow us to conclude that ShengGuZaiZaoSan can increase bone resorption and accelerate bone remodeling by increasing osteoclast numbers at the former stage and can enhance osteoclast function at the latter stage. These changes are beneficial to fracture healing.
Animals ; Bone Remodeling ; drug effects ; Bone Resorption ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Fracture Healing ; drug effects ; physiology ; Male ; Osteoclasts ; drug effects ; pathology ; Phytotherapy ; Rabbits ; Radius Fractures ; drug therapy ; pathology ; physiopathology ; Random Allocation

Dental implant is an advanced prosthodontic treatment widely accepted by patients with missing tooth. However, peri-implant bone loss is still an important reason which limits wider application of the implants to a certain extent. Bisphosphonates is an osteoclastic bone resorption inhibitor that is widely used in clinical practice with the function of inhibiting bone resorption and increasing bone density. As the defect of systemic BPs treatment, local application of BPs in implant has become a research hotspot recently. Calcium phosphate ceramics, polylactic acid, fibrinogen film and collagen membrane have been reported as BPs carriers. This article summarizes the researches on the mechanism of bone regulation and local delivering system of BPs.
Administration, Topical ; Bone Density Conservation Agents ; administration & dosage ; Bone Remodeling ; drug effects ; physiology ; Dental Implantation, Endosseous ; methods ; Dental Implants ; Diphosphonates ; administration & dosage ; Humans

AIMTo determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-beta1 (TGF-beta1), bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) in the tooth sockets of rat.

METHODOLOGYForty-eight male Wistar rats were randomly divided into experimental and control groups (n = 24). Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-beta1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation.

RESULTSThe fusiform stroma cells in the tooth extraction socket began to express TGF-beta1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-beta1 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group.

CONCLUSIONThe findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.

Alveolar Process ; drug effects ; Animals ; Bone Morphogenetic Protein 2 ; analysis ; drug effects ; Bone Remodeling ; drug effects ; Drug Carriers ; Endothelial Cells ; drug effects ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; In Situ Hybridization ; Lactic Acid ; Male ; Mandible ; drug effects ; Osteoblasts ; drug effects ; Osteogenesis ; drug effects ; Polyglycolic Acid ; RNA, Messenger ; analysis ; drug effects ; Random Allocation ; Rats ; Rats, Wistar ; Simvastatin ; pharmacology ; Stromal Cells ; drug effects ; Time Factors ; Tooth Socket ; drug effects ; Transforming Growth Factor beta1 ; analysis ; drug effects ; Up-Regulation ; drug effects ; Vascular Endothelial Growth Factor A ; analysis ; drug effects

OBJECTIVETo study the effects of low pre-pregnant lead exposure level on the mobilization of lead and calcium in maternal skeleton during gestation and lactation in mice.

METHODSSeventy Kunming female mice were randomly divided into the lead exposure or control groups, 36 mice were exposed to lead by drinking water (50 mg/L) and 36 mice were exposed to deionized water for 4 weeks. The levels of calcium and lead in blood and femurs were measured on the 1st, 7th and 14th days during gestation and on the 1st,10th and 21st days during lactation with atomic absorption spectrophotometry using a heated graphite atomizer or flame atomic absorption spectrophotometry.

RESULTSAs compared with the pre-pregnant, at the end of lactation in exposure group the levels of calcium in blood and bones significantly decreased 18.5% and 17.75%, respectively, the levels of lead in blood significantly increased 65.22% and the levels of lead in bones significantly decreased 28.45% (P < 0.05). There was a significant negative correlation between the blood lead level and the bone lead level during gestation and lactation in exposure group (r = -0.904, P < 0.01). There were significant differences of lead and calcium levels during the gestation and lactation between exposure group and control group (P < 0.05).

CONCLUSIONThe lead mobilization in maternal bone occurred during gestation and lactation in mice, which could be accelerated by the low pre-pregnant lead exposure.

Animals ; Bone Remodeling ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Calcium ; blood ; metabolism ; Calcium, Dietary ; Female ; Lactation ; Lead ; blood ; toxicity ; Mice ; Mice, Inbred Strains ; Pregnancy ; Prenatal Exposure Delayed Effects

OBJECTIVE: To examine the effects of ursolic acid (UA) on mitigating retinoic acid (RA)-induced osteoporosis in rats. METHODS: Fifty female Sprague-Dawley rats were randomly divided into the control group (n=10) and the osteoporosis group (n=40). The 40 osteoporosis rats were induced by 75 mg/(kg•d) RA once daily for 2 weeks, and then were randomly assigned to vehicle control (model), low-, middle-, and high-dose UA [(UA-L, UA-M, UA-H; 30, 60, 120 mg/(kg•d), respectively] groups (10 rats each). UA were administered once daily to the rats from the 3rd weeks for up to 4 weeks by gavage. Bone turnover markers [serum alkaline phosphatase (ALP), osteocalcin (OCN), urine deoxypyridinoline (DPD)] and other parameters, including serum calcium (S-Ca), serum phosphorus (S-P), urine calcium (U-Ca), urine phosphorus (U-P), and bone mineral density (BMD) of the femur, 4th lumbar vertebra and tibia, bone biomechanical properties and trabecular microarchitecture, were measured. RESULTS: The osteoporosis in rats was successfully induced by RA. Compared with the model group, UA-M and UA-H significantly reversed the RA-induced changes in S-P, U-Ca, U-P, ALP, OCN and urine DPD ratio and markedly enhanced the BMD of right femur, 4th lumbar vertebra and tibia (Plt;0.05 or Plt;0.01). Further, biomechanical test and microcomputed tomography evaluation also showed that UA-H drastically improved biomechanical properties and trabecular microarchitecture (Plt;0.05 or Plt;0.01). CONCLUSION UA could promote bone formation, increase osteoblastic activity and reduce osteoclastic activity in rats, indicating that UA might be a potential therapeutic of RA-induced acute osteoporosis.
Animals ; Biomechanical Phenomena ; Bone Density ; drug effects ; Bone Remodeling ; drug effects ; Female ; Osteoporosis ; diagnostic imaging ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Tretinoin ; toxicity ; Triterpenes ; pharmacology ; therapeutic use ; X-Ray Microtomography

OBJECTIVETo investigate the association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride(RLX) on bone mineral density (BMD) and bone turnover markers in postmenopausal women with osteoporosis.

METHODSA total of 68 unrelated postmenopausal women with osteoporosis of Han ethnicity aged 47-74 years were randomly divided into 2 groups of 34 women: RLX group (60 mg were given daily for 12 months) and placebo group. BMD and bone turnover markers were measured at baseline, 6 and 12 months after treatment. The polymorphisms of Xba I and Pvu II sites in estrogen receptor 1 gene(ESR1), Ras I site in ESR2 gene, and start codon (Fok I) and CDX2 binding sites in vitamin D receptor gene (VDR) were analyzed.

RESULTSA total of 58 patients completed 12 months of study period. By the end of study, the increased percentage of BMD in lumbar spine 2-4 (L2-4), total hip, and trochanter were found significantly different between RLX group and placebo group(P<0.05), and the decreased percentage of C-telopeptide and osteocalcin were significantly different between the two groups (P<0.01). The BMD of total hip and trochanter of women with FF genotypes of VDR Fok I site were decreased by 1.98%+/-4.86% and 2.26%+/-4.73% respectively in the RLX group, but those of women with Ff/ff genotypes were increased by 2.52%+/-2.75% and 2.74 %+/-2.97%, respectively(P<0.05). Moreover, the total hip BMD of women with PP/Pp genotypes of ESR1 Pvu II site was increased by 2.12%+/-2.78%, and of women with pp genotype it was decreased by 1.34%+/-3.73%(P<0.05). However, no significant association was observed of the polymorphisms of five sites with the changes of BMD and bone turnover markers in the placebo group.

CONCLUSIONThe effect of RLX on BMD in postmenopausal women with osteoporosis is regulated by the polymorphisms of Fok I of VDR gene and Pvu II of ESR1 gene. The study is valuable to select this drug according to genotype of patients in clinical.

Aged ; Biomarkers ; metabolism ; Bone Density ; drug effects ; genetics ; Bone Diseases, Metabolic ; genetics ; metabolism ; Bone Remodeling ; drug effects ; genetics ; Bone and Bones ; drug effects ; Double-Blind Method ; Female ; Humans ; Middle Aged ; Osteoporosis ; drug therapy ; Osteoporosis, Postmenopausal ; drug therapy ; Polymorphism, Genetic ; Postmenopause ; drug effects ; Raloxifene Hydrochloride ; pharmacology ; therapeutic use ; Selective Estrogen Receptor Modulators ; pharmacology ; Women

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) act by irreversibly binding to the H+-K+-ATPase of the proton pump in parietal cells and may possibly affect the vacuolar H+-ATPase in osteoclasts. METHODS: We investigated the effect of 8 weeks of PPI treatment on the parameters of bone turnover and compared PPI with revaprazan, which acts by reversibly binding to H+-K+-ATPase in proton pumps. This study was a parallel randomized controlled trial. For 8 weeks, either a PPI or revaprazan was randomly assigned to patients with gastric ulcers. The parameters of bone turnover were measured at the beginning of and after the 8-week treatment period. RESULTS: Twenty-six patients (PPI, n=13; revaprazan, n=13) completed the intention-to-treat analysis. After the 8-week treatment period, serum calcium and urine deoxypyridinoline (DPD) were increased in the PPI group (serum calcium, p=0.046; urine DPD, p=0.046) but not in the revaprazan group. According to multivariate linear regression analysis, age > or =60 years was an independent predictor for the changes in serum calcium and urine DPD. CONCLUSIONS: In elderly patients, administering a PPI for 8 weeks altered bone parameters. Our study suggested that PPIs might directly alter bone metabolism via the vacuolar H+-ATPase in osteoclasts.
Aged ; Amino Acids/drug effects/urine ; Bone Remodeling/*drug effects ; Bone and Bones/*metabolism ; Calcium/blood ; Female ; Humans ; Intention to Treat Analysis ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Osteoclasts/*metabolism ; Prospective Studies ; Proton Pump Inhibitors/*pharmacology ; Pyrimidinones/*pharmacology ; Tetrahydroisoquinolines/*pharmacology