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At least 1,009 records · Page 56Linked to original sources
PubMed2004

Both resistance and agility training increase cortical bone density in 75- to 85-year-old women with low bone mass: a 6-month randomized controlled trial.

A randomized, controlled, single-blinded 25-wk prospective study was conducted to compare the effects of group-based resistance and agility training on bone, as measured by both dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), in older women with low bone mass. Ninety-eight community-dwelling women aged 75-85 yr were randomized to one of three experimental groups: resistance training (n = 32), agility training (n = 34), or stretching (sham exercise) (n = 32). Total hip, femoral neck, and trochanteric bone mineral density (BMD) were measured by DXA. Peripheral QCT measurements were performed at the tibia and radius. The pQCT outcome measures at the shaft regions were cortical bone content, cortical bone cross-sectional area, cortical bone density, and density-weighted polar section modulus (SSI). The pQCT outcome measures at the distal sites were total bone content, total bone cross-sectional area, and total bone density. At trial completion, the agility training group significantly increased cortical bone density by 0.5 +/- 0.2% (SE) at the tibial shaft compared with a 0.4 +/- 0.3% loss in the stretching group. The resistance training group significantly increased cortical bone density (1.4 +/- 0.6%) at the radial shaft compared, with a 0.4 +/- 0.5% loss in the agility training group. No significant between-group differences were observed in the other bone outcome measures (by DXA or pQCT). Future research is needed to determine the mechanism(s) responsible for the observed adaptation of the cortical bone to mechanical loading.

Absorptiometry, Photon↗
PubMed2006

Biochemical markers of bone turnover and their relation to forearm bone mineral density in persons of Pakistani and Norwegian background living in Oslo, Norway: The Oslo Health Study.

OBJECTIVE: To evaluate whether Pakistanis have increased bone turnover compared with ethnic Norwegians due to their high prevalence of vitamin D deficiency and secondary hyperparathyroidism, and whether the relation between bone turnover and bone mineral density (BMD) differs between Pakistanis and ethnic Norwegians. DESIGN: A cross-sectional, population-based study conducted in the city of Oslo in 2000-2001. Random samples of 132 community-dwelling Pakistani men and women of ages 40, 45, and 59-60 years, and 580 community-dwelling Norwegian men and women of ages 45 and 59-60 years are included in this substudy. METHODS: Venous serum samples were drawn for measurements of markers of the vitamin D endocrine system and the bone turnover markers osteocalcin (s-OC), bone alkaline phosphatase (s-bone ALP), and tartrate-resistant acid phosphatase (s-TRACP). BMD was measured at the forearm by single-energy X-ray absorptiometry. RESULTS: Pakistanis had higher s-bone ALP compared with Norwegians. Mean (95% CI) age-adjusted levels were 22.5 (21.0, 24.1) U/l in Pakistani men versus 19.3 (18.6, 20.1) U/l in Norwegian men, P < 0.0005, and 20.3 (18.4, 22.1) U/l in Pakistani women versus 16.7 (16.0, 17.4) U/l in Norwegian women, P = 0.001. There tended to be an inverse association between bone turnover and BMD in men and women of both ethnic groups, and it was strongest for s-bone ALP. Overall mean (95% CI) distal BMD decrease was -16 (-20, -11) mg/cm(2) per 1 s.d. increase in s-bone ALP (P < 0.0005) when adjusting for age, sex, and ethnicity. CONCLUSIONS: Except for somewhat higher s-bone ALP levels in Pakistanis, there were only minor ethnic differences in bone turnover, despite a strikingly different prevalence of secondary hyperparathyroidism. Bone turnover was inversely associated with forearm BMD in both ethnic groups.

Acid Phosphatase↗
PubMed2005

Bone response to submerged, unloaded implants inserted in poor bone sites: a histological and histomorphometrical study of 8 titanium implants retrieved from man.

An important parameter that influences the long-term success of oral implants is the bone quality of the implant bed. Posterior areas of the jaws have been avoided in implant dentistry because of their poor bone quality, higher chewing forces, and presumed higher implant failure rates. Several researchers have deemed soft bone implant sites to be a great potential risk situation, and most failures have been found in sites where the bone density was already low. The inferior success rates in the posterior maxilla have been attributed to a lower bone density and a lesser bone-implant interface. The aim of the present study was a histological and histomorphometrical analysis of the bone response to submerged implants inserted in posterior areas of the human jaws and retrieved, for different causes, after healing periods varying from 6 weeks to 12 months. Eight submerged implants that had been retrieved for different causes after different healing periods were evaluated in the present study. All implants were submerged and unloaded. Three implants had been removed for inadequate patient adaptation, 2 for inability of the implant to meet changed prosthetic needs, 1 for not optimal position from esthetic and hygiene aspects, and the last 2 for pain and dysesthesia. All the implants were retrieved with a 5-mm trephine bur. Newly formed peri-implant bone was found in all implants even after shorter healing periods. The bone-implant contact percentage varied from 30% to 96%. In conclusion, some surfaces have an improved characteristic of contact osteogenesis in soft bone, with coverage of the implant surface with a bone layer as a base for intensive bone formation and remodeling. We documented osseointegration of implants with a rough surface even after an insertion period of less than 2 months, both in the mandible and in the maxilla. From these results, we tentatively extrapolate that these implants might be carefully loaded after 2 months of healing, even when inserted in soft bone. A higher removal torque value might lead to a more predictable use of shorter implants, to a support of a prosthesis with fewer implants, or to shorter healing periods.

Alveolar Bone Loss↗
PubMed2003

Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma.

PURPOSE: Increased bone resorption is a hallmark of multiple myeloma and is attributable to osteoclast activation. Recent studies showed that the receptor activator of nuclear factor kappaB ligand (RANKL) is the key mediator of osteoclastogenesis and plays a crucial role in bone destruction in malignant bone disease. We found that human myeloma cells express RANKL and analyzed the association of the RANKL expression with the presence of osteolytic bone disease in patients with multiple myeloma. EXPERIMENTAL DESIGN: Flow cytometry was performed on bone marrow samples derived from controls and multiple myeloma patients with or without osteolytic bone lesions on conventional radiography. Plasma cells were identified as CD38++/CD138+ cells. The level of RANKL expression on the surface of bone marrow plasma cells was correlated with the bone status of the patients. RESULTS: The bone marrow plasma cells from controls showed no or only a weak surface expression of RANKL, and the median mean fluorescence index (MFI) was 6. In contrast, expression of RANKL could be detected on bone marrow plasma cells from all of the patients with multiple myeloma, and median MFI was 47. The difference in MFI for RANKL expression of bone marrow plasma cells from controls and myeloma patients was highly significant (P < 0.0005). Myeloma patients with osteolytic bone lesions showed a significantly higher expression of RANKL (median MFI = 60; range, 16-2494) compared with patients without osteolysis (median MFI = 16; range, 6-229; P < 0.0005). CONCLUSIONS: These results show for the first time that the level of RANKL expression by myeloma cells correlates significantly with osteolytic bone disease.

ADP-ribosyl Cyclase↗
PubMed2003

[Experimental study of repairing segmental bone defect with reconstituted freeze-dried bone allograft].

OBJECTIVE: To study the effect of basic fibroblast growth factor (bFGF) and hyaluronic acid gel (HAG) combined with freeze-dried bone allograft in repairing segmental bone defect and to explore their mechanism. METHODS: The 15 mm segmental bone/periosteum defects were created on bilateral radius in 50 New Zealand rabbits and were treated with four different kinds of implants on 25 radius respectively (group A: bFGF and HAG combined with freeze-dried bone; group B: bFGF combined with freeze-dried bone; group C: HAG combined with freeze-dried bone; group D: simple freeze-dried bone as a control). The repair of defect was observed radiologically and histologically and were analyzed by radionuclide bone imaging and measurement of calcium contents at different periods. RESULTS: The new bone formation, bone metabolic activity and calcium contents of defects were higher in group A than in group B (P < 0.05), and were higher in group B than in groups C and D (P < 0.05). There were no significant difference between groups C and D. The bone defects healed in the 8th week in group A, in the 10th week in group B, but did not healed in the 10th week in groups C and D. CONCLUSION: As an osteogenetic factor, bFGF promotes the new bone formation; as a slow-release carrier, HAG enhances the effectiveness of bFGF. The combination of bFGF, HAG and freeze-dried bone allograft can repair the segmental bone defect more effectively.

Animals↗
PubMedDate not supplied

Clinical value of bone remodelling markers in patients with bone metastases treated with zoledronic acid.

BACKGROUND: Bisphosphonates have an established role in the treatment of bone metastases from a variety of solid tumours. The objective response to anti-resorptive treatment cannot be evaluated by imaging techniques. A number of bone remodelling markers have been associated with bone metastases status; among them, urine and serum levels of N-terminal telopeptide of collagen type I (NTx) seem to have the best diagnostic accuracy. However, serum NTx has not yet been properly evaluated. PATIENTS AND METHODS: Seventy-one consecutive patients with newly diagnosed skeletal metastases were enrolled in this prospective study. All of them were treated with zoledronic acid at 4 mg, every 3 or 4 weeks. Serum NTx and bone-isoform of alkaline phosphatase (BAP) were measured by enzyme-linked immunosorbent assays at baseline and every 2 months thereafter. RESULTS: At baseline, serum NTx and BAP levels were significantly higher in patients with blastic than lytic bone lesions and in those with multiple rather than few bone site involvement. Forty-seven patients were followed for a median period of 139 days. Zoledronic acid resulted in a significant NTx reduction at first and second post-treatment evaluations (mean reduction of 43% at first evaluation); thereafter, mean NTx levels remained suppressed. In contrast, BAP levels did not show any significant changes. Bone disease progression resulted in a significant NTx elevation by an average of 69%. The initial response of NTx to zoledronic acid was correlated with the long-term clinical outcome of bone disease: patients with an initial NTx elevation had a significantly higher rate of bone disease progression compared to those with an initial NTx decline (66.7% versus 18.8%, p=0.001). Extraskeletal disease or bone irradiation did not influence NTx response. CONCLUSION: Serum NTx appears to be a useful marker in monitoring patients with skeletal metastases, as it is correlated with the type and bulk of bone disease and reflects bone disease progression. It is also useful in monitoring bisphosphonate therapy, while the initial response to this therapy seems to bear a prognostic significance for bone disease outcome.

Aged↗
PubMed2006

[Evaluation of cancer-induced bone diseases by bone metabolic marker].

Recently, several new bone metabolic markers have been developed and applied for diagnosis of bone metastasis. We have investigated the efficacy of several bone metabolic markers : serum carboxy-terminal telopeptide of type 1 collagen ( I CTP), C-terminal cross-linked telopeptide of type I collagen (CTX) and urinary free deoxypyridinoline (fDPD) as bone resorption markers, serum carboxy-terminal propeptide of type 1 collagen (P I CP), osteocalcin (OC), and bone alkaline phosphatase (BAP) as bone formation markers for diagnosis of bone metastasis. I CTP was most useful for diagnosis of bone metastasis in breast cancer patients because of no increase in postmenopausal osteoporosis. Combination of resorption and formation markers increased sensitivity. In follow-up, bone metabolic markers seemed more useful for predicting therapeutic response of bone metastasis than tumor markers. Bone metabolic markers were also useful for predicting survival or occurrence of skeletal-related events. These findings suggest that bone metabolic markers would be useful to detect, to monitor, and to predict prognosis of bone metastases.

Alkaline Phosphatase↗
PubMed1990

Bone morphogenetic protein-mediated interaction of periosteum and diaphysis. Citric acid and other factors influencing the generation of parosteal bone.

In rabbits, after long-bone growth is complete and the cambium layer regresses, mesenchymal-type cells with embryonic potential (competence) for bone development persist in the adventitial layer of periosteum. These cells are not determined osteoprogenitor cells (stem cells) because bone tissue differentiation does not occur when adult periosteum is transplanted into a heterotopic site. In this respect, adventitial cells differ from bone marrow stroma cells. In a parosteal orthotopic site in the space between the adult periosteum and diaphysis, implants of bone morphogenetic protein (BMP) and associated noncollagenous proteins (BMP/NCP) induce adventitia and adjacent muscle connective-tissue-derived cells to switch from a fibrogenetic to a chondroosteoprogenetic pattern of bone development. The quantity of induced bone is proportional to the dose of BMP/NCP in the range from 10 to 50 mg; immature rabbits produced larger deposits than mature rabbits in response to BMP/NCP. Preoperative local intramuscular injections of citric, edetic, or hyaluronic acids in specified concentrations markedly enhanced subperiosteal BMP/NCP-induced bone formation. The quantity of bovine or human BMP/NCP-induced bone formation in rabbits is also increased by very low-dose immunosuppression but not by bone mineral, tricalcium phosphate ceramic, inorganic calcium salts, or various space-occupying, unspecific chemical irritants. Although composities of BMP/NCP and allogeneic rabbit tendon collagen increased the quantity of bone in a parosteal site, in a heterotopic site the composite failed to induce bone formation. In a parosteal site, the conditions permitting BMP/NCP-induced bone formation develop, and the end product of the morphogenetic response is a duplicate diaphysis. How BMP reactivates the morphogenetic process in postfetal mesenchymal-type adventitial cells persisting in adult periosteum (including adjacent muscle attachments) is not known.

Animals↗
PubMed1989

[An in vivo study of inorganic bone particle-impregnated bone cement].

According to definite proportion by weight, inorganic bone particles were impregnated into bone cement and then used for the fixation of implanted artificial femoral head in a series of canines. Upon successive observations, new bone was seen to have already been growing into the bone cement one month post operatively, and active growth going on with bone tissue passing through the whole layer of cement three months after operation. In the fifth month's specimens, most of the inorganic bone particles were replaced by new bone tissue while slices of one year post operation showed that the bone tissue was mature and the activity of bone formation ceased. The biological fixation effect produced by bone ingrowth was found to have increased the shearing strength of cement-bone interface to 1.4-3.6 times of the control side and the stability of prosthesis was improved obviously. The bone-particle-impregnated bone cement has already been using in our clinical practice since 1987.

Animals↗
PubMed1998

Angiogenesis inhibitor TNP-470 inhibits human breast cancer osteolytic bone metastasis in nude mice through the reduction of bone resorption.

Angiogenesis inhibitor TNP-470, 6-O-(N-chloroacetyl-carbamoyl)-fumagillol, semisynthetic analogue of fumagillin, has strong inhibitory activities against in vivo tumor growth and metastasis in a wide variety of tumors. However, it is still unknown whether this agent inhibits bone metastasis. We examined the effects of TNP-470 in a bone metastasis model in nude mice in which intracardiac injection of the human breast cancer cell line MDA-MB-231 (MDA-231) produced osteolytic bone metastasis. After inoculation of MDA-231 cells into the left heart ventricle, TNP-470 (30 mg/kg, three times a week) or PBS was s.c. administrated for 4 weeks. After this period, the TNP-470 had reduced not only the number and area of osteolytic bone metastases (approximately 60 and 70%, respectively) but also their radiolucency. Histological examination of the femurs of the untreated group revealed that most of the cancellous bone had been replaced by the metastatic cancer. Numerous active osteoclasts were present along the trabecular bone surface surrounded by the metastatic MDA-231 cancer cells aggressively invading the bone marrow. In contrast, in the bone from TNP-470-treated mice, bone destruction was markedly inhibited, and there were much fewer osteoclasts. In a murine bone marrow culture under 1,25-dihydroxyvitamin D3 in which mature functional osteoclasts formed in vitro, TNP-470 significantly inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cells. And also, TNP-470 suppressed the in vivo bone resorption in calvaria treated with interleukin-1beta, an osteoclast stimulator. These data suggested that TNP-470 inhibited bone metastasis through not only antitumor action by its angiogenesis inhibition but also by the inhibition of osteoclastic bone resorption. Our results indicate that TNP-470 should be a potentially beneficial drug to be used in the treatment of osteolytic metastasis.

Animals↗
PubMed2006

Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease.

Minimal trauma fractures in bone diseases are the result of bone fragility. Rather than considering bone fragility as being the result of a reduced amount of bone, we recognize that bone fragility is the result of changes in the material and structural properties of bone. A better understanding of the contribution of each component of the material composition and structure and how these interact to maintain whole bone strength is obtained by the study of metabolic bone diseases. Disorders of collagen (osteogenesis imperfecta and Paget's disease of bone), mineral content, composition and distribution (fluorosis and osteomalacia); diseases of high remodeling (postmenopausal osteoporosis, hyperparathyroidism, and hyperthyroidism) and low remodeling (osteopetrosis, pycnodysostosis); and other diseases (idiopathic male osteoporosis, corticosteroid-induced osteoporosis) produce abnormalities in the material composition and structure that lead to bone fragility. Observations in patients and in animal models provide insights on the biomechanical consequences of these illnesses and the nature of the qualities of bone that determine its strength.

Animals↗
PubMed1985

The value of the bone scan and bone marrow biopsy staging small cell lung cancer.

The charts of 112 patients with small cell lung cancer were reviewed in a retrospective fashion in order to define the role of the radionuclide bone scan and bone marrow biopsy in the staging of this disease. Both a radionuclide bone scan and bone marrow biopsy were performed on all patients at the time of diagnosis. Sixty-one percent of patients had a negative bone scan and negative biopsy; 22% had a positive bone scan and negative biopsy; 8% had a negative scan and positive biopsy; and 9% had a positive scan and positive biopsy. In 21 of the 44 patients with osseous involvement, no other focus of distant metastasis was found. The bone scan showed greater than or equal to 3 areas of increased uptake in 15 patients, 2 areas of increased uptake in 13 patients, and 1 area in 7 patients. The number of patients with bone marrow biopsy results positive for tumor in these 3 groups were 5, 3, and 2, respectively. Our study shows a lack of correlation between bone scan and bone marrow biopsy results. The bone scan and bone marrow biopsy identify independent patterns of osseous metastasis. Both procedures should be performed in the evaluation of patients with small cell lung cancer.

Biopsy↗
PubMed1996

Bone mineralization and bone mineral metabolism in children with juvenile rheumatoid arthritis.

OBJECTIVE: To identify mechanisms of the osteopenia associated with juvenile rheumatoid arthritis (JRA) by determining parameters of bone mineralization, and bone mineral content and density (BMC and BMD), in children with JRA. METHODS: BMC and BMD were measured by dual x-ray absorptiometry in 41 children with JRA and 62 healthy children. Serum samples were analyzed for concentrations of minerals, vitamin D, parathyroid hormone, osteocalcin, bone-specific alkaline phosphatase (BAP), procollagen I carboxy-terminal propeptide, and tartrate-resistant acid phosphatase (TRAP), and urinary excretion of deoxypyridinoline crosslinks and calcium. RESULTS: BMD was decreased in all sites in JRA patients. BMD, corrected for age, height, weight, and bone area, was decreased at cortical bone sites (1/3 radius, upper and lower extremities, and whole body). Low concentrations of osteocalcin and BAP suggested reduced bone formation, and low TRAP levels suggested decreased resorption. Clinical scales of disease severity were negatively correlated with measures of bone mass. Laboratory markers of disease severity were highly correlated with decreases in markers of bone formation, but not with those of resorption. Although laboratory findings were similar for children with oligoarticular and polyarticular disease, differences in bone mass were greater in children with polyarticular disease. CONCLUSION: These data suggest an association between decreased bone mineralization in JRA and low bone formation that is related to disease severity. Efforts to stimulate bone formation, therefore, need to be considered clinically in prepubertal children with active JRA.

Adolescent↗
PubMed1990

Bone resorption in orthotopic and heterotopic bone of dichloromethylene bisphosphonate-treated rats.

The effect of the bisphosphonate dichloromethylene bisphosphonate (Cl2MBP) on orthotopic and heterotopic bone, induced by implants of demineralized bone matrix (DBM) in rats, was analyzed, with special reference to bone resorption. The heterotopic bone was formed by induction for 3 weeks; at this time, the rats were given daily subcutaneous injections of 3 mg/kg of body weight of Cl2MBP or saline, until sacrifice. Prior to the start of treatment, the animals were given 45Ca and [3H]proline to label the inorganic and organic components of bone, respectively. Groups of rats were sacrificed at intervals from 1 to 31 days after isotope injection, and the net formation of bone and the elimination rates of the two isotopes were studied in the heterotopic bone, in diaphyseal and metaphyseal bone, and in teeth. The treatment with Cl2MBP caused a doubling of the daily net increase in mineral of the induced heterotopic bone, and a less pronounced increase in the ash content of tibiae. The treatment decreased the elimination rates of both isotopes in the orthotopic and heterotopic bone, showing that decreased bone resorption is the cause of the increased net bone formation.

Animals↗
PubMed2000

Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model.

A study was performed in dogs to evaluate the dose-response characteristics and effectiveness of recombinant human bone morphogenetic protein-2 with a collagen sponge carrier in a segmental defect model. Twenty-seven dogs underwent bilateral radial osteotomies with creation of a 2.5-cm diaphyseal defect. All received autogenous cancellous bone graft in one defect and a collagen implant in the other. These implants contained recombinant human bone morphogenetic protein-2 at the following doses: group 1 at 0 microg (three dogs, 0 microg/ml total implant volume), group 2 at 150 microg (three dogs, 50 microg/ml), group 3 at 600 ,g (three dogs, 200 microg/ml), group 4 at 2,400 microg (three dogs, 800 microg/ml), group 5 at 0 microg (five dogs, 0 microg/ml), group 6 at 150 microg (five dogs, 200 microg/ml), and group 7 at 600 microg (five dogs, 50 microg/ml). The defects were stabilized with external fixators. The dogs in groups 1-4 were killed at 12 weeks postoperatively, and those in groups 5-7 were killed at 24 weeks postoperatively except for one dog in group 7, which was killed at 48 weeks. Evaluation included monthly radiographs, biomechanical testing, and nondemineralized histology. All 27 radii with autogenous cancellous bone graft and all 19 implants treated with recombinant human bone morphogenetic protein-2 achieved radiographic and histologic union and gross stability. The eight radii treated with collagen carrier alone went on to radiographic and histologic nonunion and were grossly unstable at death. A dose-dependent occurrence of cyst-like bone voids was noted radiographically and histologically. Biomechanical performance tended to be better at the lowest dose studied at 12 weeks, and all three doses performed better than the placebo (p < 0.05) at 12 and 24 weeks. By 24 weeks, radiolucent areas corresponding to histologic bone voids persisted radiographically, although there was evidence of early bone remodeling. This remodeling progressed to 48 weeks in the single animal followed to this time point, although bone voids remained. These radiologic findings were confirmed histologically. Recombinant human bone morphogenetic protein-2 in a collagen sponge carrier has significant osteoinductive activity in this canine segmental defect model. A dose-response relationship is evident, with heterotopic bone and cyst-like void formation at higher doses and a minimum effective dose of 0-150 microg. At 12 and 24 weeks postoperatively, biomechanical parameters achieved by defects treated with recombinant human bone morphogenetic protein-2 were comparable with those of autograft controls and were significantly stronger than those of the placebo (p < 0.05).

Animals↗
PubMed1994

Acute effects of high-dose chemotherapy followed by bone marrow transplantation on serum markers of bone metabolism.

There is an interplay between the cells in the bone marrow and the surrounding bone tissue, but little is known about the effects of myeloablative treatment followed by bone marrow transplantation on bone metabolism. We have therefore investigated 24 patients undergoing bone marrow transplantation (14 autologous, 10 allogeneic) for hematological malignancies. Serum concentrations of parathyroid hormone (PTH), albumin-modified calcium, and biomarkers for bone turnover--osteocalcin, bone alkaline phosphatase (B-ALP), and carboxyterminal cross-linked telopeptide of type I collagen (ICTP)--were measured. The samples were collected before myeloablative treatment, on the day of bone marrow infusion and 1, 2, 3, and 12 weeks thereafter. A serum PTH peak was consistently seen the day after total body irradiation, but no long-term effects on PTH/calcium homeostasis were observed. Bone formation as reflected by serum osteocalcin and B-ALP decreased, with nadir levels 2 to 3 weeks after marrow infusion. A simultaneous increase in bone resorption (increased S-ICTP) occurred. Pretreatment values were not completely regained 12 weeks after transplantation. The findings indicate that bone tissue is affected by myeloablative treatment, and the changes in biomarkers imply a net loss of bone over the study period.

Adolescent↗
PubMed1991

Inhibition of bone resorption by bisphosphonates: interactions between bisphosphonates, osteoclasts, and bone.

Bisphosphonates are nonbiodegradable pyrophosphate analogues that are being used increasingly to inhibit bone resorption in disorders characterized by excessive bone loss. We have previously found that dichloromethylene bisphosphonate (Cl2MBP) inhibits bone resorption through injury to the cells that resorb Cl2MBP-contaminated surfaces. 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP) is a more potent inhibitor of bone resorption in vivo, and we have attempted to identify a step in the resorptive pathway that accounts for this increased potency. We found that when osteoclasts, isolated from neonatal rat long bones, were incubated on bone slices in the presence of bisphosphonates, AHPrBP was less, rather than more potent as a resorption-inhibitor than Cl2MBP. The greater sensitivity of resorption to AHPrBP in vivo could neither be attributed to an effect of AHPrBP on the ability of osteoblastic cells to stimulate resorption in response to calcium-regulating hormones in vitro nor to an effect on osteoclast generation: osteoclast formation was unaffected by concentrations of AHPrBP 10-fold higher than those of Cl2MBP which inhibit bone resorption in the bone slice assay. We also found no evidence for impaired osteoclast generation in vivo in AHPrBP-treated rats. These results suggest that the comparisons of potency in vitro do not include all the factors responsible for determining bisphosphonate potency in vivo. Because bisphosphonates owe the specificity of their actions to their ability to bind to bone surfaces, we performed experiments using bone slices that had been immersed in bisphosphonates before use. Bone resorption was virtually abolished on bone slices preincubated in 10(-3) M AHPrBP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Bone microarchitecture as an important determinant of bone strength.

Structure and microarchitecture are determinant aspects of bone strength and essential elements for the assessment of bone mechanical properties. The main structural determinants of bone mechanical strength include width and porosity in the cortical bone; shape, width, connectivity, and anisotropy in the trabecular bone. There are several methods to assess bone architecture, particularly at the trabecular level. Two different approaches can be identified. The first is based on the use of optical microscopy and on the principles of quantitative histology, which evaluate microarchitecture two-dimensionally. The second applies the most modern diagnostic techniques, employing computed tomography and magnetic resonance to obtain and analyze three-dimensional images. From a clinical point of view, microarchitecture is an interesting aspect to study and define specific patterns, such as glucocorticoid-induced osteoporosis, or to evaluate bone alterations in transplanted patients. Microarchitecture seems to be a determinant of bone fragility independent of bone density. Moreover, bone microarchitecture seems to be important to understand the mechanisms of bone fragility as well as the action of the drugs used to prevent osteoporotic fractures. Several in vivo studies (on animals and humans) showed important findings on the effects of different treatments on microarchitecture. Bisphosphonates and parathyroid hormone seemed to preserve or even improve microarchitecture. These observations can provide an additional interpretation for the anti-fracture effect of drugs from a structural viewpoint. The challenge for the future will be to evaluate bone quality in vivo with the same or better resolution and accuracy than the invasive methods in use today.

Biomechanical Phenomena↗