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PubMed1998

Effect of long-term treatment with GH on bone metabolism, bone mineral density and bone elasticity in GH-deficient adults.

OBJECTIVE: Adults with GH deficiency (GHD) commonly have subnormal bone mineral density (BMD), and have been reported to have an increased risk of fractures. It has been suggested that GH replacement therapy may have beneficial effects on bone in such patients. The aim of this study was to investigate the effects of long-term GH replacement therapy on bone metabolism, BMD and bone elasticity in adults with GHD. DESIGN: At the start of the study, 20 adults with GHD were randomized to receive either GH, 0.25 IU/kg/week (the 'GH group') or placebo (the 'placebo group'). After 6 months, patients in the placebo group were switched to GH therapy, and all patients received GH for a further 42 months. PATIENTS: Of the 20 patients included in the study, 11 were male and nine were female. Mean age at the start of the study was 42.5 +/- 10.1 years. All patients had been GH-deficient for at least 2 years before the start of the study. MEASUREMENTS: Rates of bone resorption and formation were assessed by measuring serum levels of type I collagen carboxyterminal cross-linked telopeptide (ICTP) and carboxyterminal propeptide of type I procollagen (PICP), respectively. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the non-dominant forearm by single-photon absorptiometry (SPA). Bone elasticity was assessed by measuring apparent phalangeal ultrasound transmission velocity (APU). RESULTS: The main results in the GH group were as follows. The rate of bone resorption increased significantly during the first 6 months of treatment and remained significantly elevated above its baseline level thereafter. The rate of bone formation also rose during the first 6 months of treatment and remained elevated thereafter, but was significantly higher than at baseline only after 24 months of treatment. At both sites measured, BMD was subnormal at baseline, decreased during the first 6 months of treatment, and increased progressively for the rest of the study, eventually rising well above its baseline level. Bone elasticity decreased during the first 6 months of treatment, but had returned to its baseline level after 24 months. CONCLUSIONS: Our results support previous findings that BMD is subnormal in adults with GHD, that GH replacement therapy can stimulate bone turnover in such adults and that, in the long term, such stimulation results in a significant increase in BMD. In addition they show, for the first time, that BMD may continue to rise even after GH replacement therapy has been administered for 4 years, and indicate that bone elasticity is not adversely affected by long-term GH therapy.

Absorptiometry, Photon↗
PubMed2004

Bone formation following sinus grafting with autogenous bone-derived cells and bovine bone mineral in minipigs: preliminary findings.

Bone formation in a sinus grafted with a cell-free scaffold requires the presence of local progenitor cells that differentiate into osteoblasts. The purpose of this study was to examine the effect of culture expanded autogenous bone-derived cells (ABC) with bovine bone mineral (BBM) on bone formation after single-stage sinus grafting in minipigs. Bone biopsies from the iliac crest were harvested 4 weeks prior to sinus grafting and ABC were culture expanded in vitro. The sinuses of five adult minipigs were grafted. In one sinus of each minipig the space between Schneider's membrane (SM) and the sinus wall was grafted with ABC (325,000 cells per sinus, on average) and BBM. In the other sinus, BBM alone was used. The animals were sacrificed after 12 weeks. One block of each grafted area was prepared by saw cutting and the amount of newly formed bone was analysed by micro-computed tomography (mu-CT). The addition of ABC to BBM significantly increased the amount of newly formed bone compared with BBM alone on mu-CT analysis (ABC+BBM: 29.86+/-6.45% vs. BBM: 22.51+/-7.28% (P=0.016)). Bone formation was increased near SM (ABC+BBM: 20.7+/-4.5% vs. BBM: 15.43+/-3.62% (P=0.009)) and in the middle zone of the grafting material (ABC+BBM: 31.63+/-7.74% vs. BBM: 22.5+/-7.91% (P=0.001)), but not near the local host bone (ABC+BBM: 37.23+/-8.23% vs. BBM: 28.42+/-12.54% (P=0.15)). These preliminary findings indicate that supplementation of cell-free grafting material with culture expanded ABC can stimulate bone formation in areas with low bone-forming capacity.

Animals↗
PubMed1996

Serum immunoreactive bone sialoprotein as a new marker of bone turnover in metabolic and malignant bone disease.

Bone sialoprotein (BSP) is a phosphorylated glycoprotein with a M(r) of 70-80 kDa that accounts for approximately 5-10% of the noncollagenous proteins of bone. Due to its relatively restricted distribution to mineralized tissues, BSP may serve as a potential marker of bone metabolism. Employing a recently developed RIA, serum BSP was measured in 133 healthy subjects, aged 20-80 yr, and in patients with primary hyperparathyroidism (pHPT; n = 26), Paget's disease of bone (PD; n = 14), untreated multiple myeloma (MM; n = 32), and breast cancer with bone metastases (BC; n = 19). Results were compared to clinical and laboratory data, including serum total alkaline phosphatase as a marker of bone formation, and the urinary cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone resorption. In healthy adults, serum BSP values ranged between 5.0-21.6 ng/mL (5-95% interval), with a median of 10.5 ng/mL (total group). In healthy females, a linear correlation was found between serum BSP and age (r = 0.51; P < 0.001), with significantly higher values in postmenopausal than in premenopausal women (13.3 +/- 4.8 vs. 9.0 +/- 3.8; P < 0.01). In the healthy group, BSP values did not change with body mass index, lumbar bone mineral density, serum calcium, serum creatinine, or serum total alkaline phosphatase levels. In contrast, a weak, but significant, correlation was observed between serum BSP and the urinary excretion of PYD and DPD. Compared to those in healthy controls, serum BSP levels were significantly higher in patients with pHPT, PD, MM, or BC (P < 0.01 for all groups). These differences remained after analyses were adjusted for age and sex. In pHPT, serum BSP levels were closely correlated to urinary PYD and DPD (r = 0.87 and 0.83, respectively; P < 0.01), whereas in PD, no correlation was observed between any of the bone markers. Serum BSP levels were highest in patients with MM, and there was a significant difference between early and advanced stages of the disease (30.2 +/- 8.0 vs. 64.3 +/- 6.8; P < 0.01). In a subgroup of 15 patients with metastatic BC, iv bisphosphonate treatment resulted in a rapid reduction of serum BSP levels to 40% of the baseline values within 4 days of treatment. In conclusion, BSP appears to be a sensitive marker of bone turnover, and the present data suggest that its serum levels predominantly reflect processes related to bone resorption.

Adult↗
PubMed1994

A comparison of demineralized freeze-dried bone and autologous bone to induce bone formation in human extraction sockets.

The purpose of this study was to test the bone-forming capacity of demineralized freeze-dried bone (DFDBA) and autologous bone grafts in extraction sockets. Seven paired sites were grafted with either DFDBA or autologous bone. The sites were reentered between 3 and 13 months for the purposes of obtaining biopsies of the grafted sites and to place endosseous implants. Biopsies from 6 of the 7 grafted sites were evaluated for new bone formation. DFDBA sites revealed the presence of dead particles of DFDBA with no evidence of bone formation on the surfaces of the implanted particles and no evidence of osteoclastic resorption of the bone particles. Biopsies from the 6 autologous sites revealed vascular channels with woven and lamellar bone. Some specimens had retained cortical, non-vital bone chips. These bone chips were undergoing active osteoclastic resorption. The results of this study questions the use of DFDBA as a bone inductive graft material.

Alveolar Process↗
PubMed2002

[Experimental study on subcutaneous bone formation by marrow stromal osteoblast-cancellous bone matrix compound artificial bone].

OBJECTIVE: To investigate the feasibility of using marrow stromal osteoblast (MSO) as bone derived cell and using cancellous bone matrix (CBM) as scaffold for bone tissue engineering, the subcutaneous osteogenesis of MSO-CBM compound artificial bone (MCCAB) was observed in the experiment. METHODS: The marrow stromal cells of adult New Zealand rabbits cultivated and induced in vitro were used to form MCCAB by mixing, seeding and solidifying methods assisted by alginate. The MCCABs were auto-transplanted subcutaneously into the rabbits for 4 to 8 weeks. The alginate-cancellous bone matrix composites or the cancellous bone matrix alone were implanted as control. The effectiveness of bone formation was assessed by means of roentgenography, histology and computerized histomorphometry. RESULTS: The osteogenesis of MCCABs was better than that of the alginate-cancellous bone matrix composites and of the cancellous bone matrixes. In the MCCABs, both intramembranous and cartilaginous osteogeneses were seen but the former was obvious. In the control, only slight cartilaginous osteogeneses were seen. CONCLUSIONS: The osteogeneses of the MCCABs constructed by using tissue engineering method were obvious when transplanted subcutaneously. The MSO and CBM can be used as good bone-derived cell and scaffold material respectively for tissue-engineered bone construction.

Animals↗
PubMed2006

Homogeneous osteogenesis and bone regeneration by demineralized bone matrix loading with collagen-targeting bone morphogenetic protein-2.

Considerable research has been focused on the development of bone morphogenetic protein-2 (BMP-2) delivery system for homologous and efficient bone regeneration. The aim of the present study was to develop a collagen-based targeting bone repair system. A collagen-binding domain (CBD) was added to the N-terminal of native BMP-2 to allow it bind to collagen specifically. We showed that the collagen-binding bone morphogenetic protein-2 (named bone morphogenetic protein2-h, BMP2-h) had maintained the full biological activity as compared to rhBMP2 lacking the CBD. In vitro functional study also demonstrated that collagen matrix could maintain higher bioactivity of BMP2-h than native BMP-2. When demineralized bone matrix (DBM) impregnated with BMP2-h was implanted subcutaneously in rats, homogeneous bone formation was observed. Moreover, in a rabbit mandible defect model, surgical implantation of collagen matrix loaded with BMP2-h exhibited remarkable osteoinductive properties and excellent homogeneous bone formation. Our studies suggested that this novel collagen-based BMP-2 targeting bone repair system induced better bone formation not only in quantity but also in quality. Similar approaches may also be used for the repair of other tissue injuries.

Animals↗
PubMed1992

Whole-body and site-specific bone remodelling in patients with previous femoral fractures: relationships between reduced physical activity, reduced bone mass and increased bone resorption.

1. A new tracer method is described for the non-invasive measurement of bone formation in the proximal femur. The method is based on our previously described whole-body method using 85Sr as the tracer (Reeve, J., Hesp, R. & Wootton, R. Calcif. Tissue Res. 1976; 22, 191-206). It allows correction to be made for long-term exchange processes within the skeleton. 2. The method has been applied in a study of regional and whole-body bone formation in 12 rehabilitated patients who had previously suffered a fracture of the proximal femur. Twelve healthy control subjects were studied, who were selected for their good health and continued physical activity. The aim was to explore the relationship between bone formation and physical activity. 3. Bone formation was similar in the two groups, both regionally and in the whole body. Based on analyses of four cadaver specimens, bone formation in the proximal femur was about one and two-thirds times that in the whole skeleton when related to mass of calcium in the region of interest. 4. Whole-body bone resorption, estimated from five measurements per subject of hydroxyproline excretion in relation to creatinine excretion, was significantly higher in the fracture patients (P < 0.01, Wilcoxon's test). 5. Estimates of current physical activity (and immediate pre-fracture physical activity) were made with a newly devised questionnaire. Historical levels of physical activity (at ages 15-45 years) were determined with Astrom's questionnaire. No bone formation index correlated with any index of physical activity. Urinary hydroxyproline excretion correlated inversely both with current physical activity and historical physical activity (for both regression coefficients P < 0.01). 6. The results are discussed in the light of our current understanding of the control of bone remodelling by the discrete basic multicellular units of bone. The opportunity to study regional bone resorption by the additional use of serial dual X-ray absorptiometry of the same region will in future allow the direct monitoring of the effects of therapeutic interventions which have been designed to prevent contralateral hip fracture.

Aged↗
PubMed2006

Function and effect of bone morphogenetic protein-7 in kidney bone and the bone-vascular links in chronic kidney disease.

In two independent and separate studies, we have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreased the serum phosphate. In the first study, the serum Ca PO(4), parathyroid hormone (PTH), and calcitriol were maintained normal after renal ablation in mice, and even mild renal injury equivalent to stage 3 CKD decreased bone formation rates. More recently, these observations were rediscovered in low-density lipoprotein receptor null (LDLR-/-) mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia and insulin resistance). We demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial calcification. We have also shown that VC is made worse by CKD and ameliorated by bone morphogenetic protein-7 (BMP-7). The finding that high-fat fed LDLR-/- animals with CKD had hyperphosphatemia which was prevented in BMP-7-treated animals lead us to examine the skeletons of these mice. It was found that significant reductions in bone formation rates were associated with high-fat feeding, and superimposing CKD resulted in the adynamic bone disorder (ABD), while VC was made worse. The effect of CKD to decrease skeletal anabolism (decreased bone formation rates and reduced number of bone modelling units) occurred despite secondary hyperparathyroidism. The BMP-7 treatment corrected the ABD and hyperphosphatemia, owing to BMP-7-driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. Thus, in the metabolic syndrome with CKD, a reduction in bone forming potential of osteogenic cells leads to the ABD producing hyperphosphatemia and VC, processes ameliorated by BMP-7, in part through increased bone formation and skeletal deposition of phosphate and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury affecting the skeleton before demonstrable hyperphosphatemia and that they are preventable and treatable. Therefore, early intervention in the skeletal disorder associated with CKD is warranted and may affect mortality of the disease.

Animals↗
PubMed1995

Comparative evaluation of bone suture anchor to bone tunnel fixation of tibialis anterior tendon in cadaveric cuboid bone: a biomechanical investigation.

A multiphase biomechanical study was performed using human tibialis anterior tendons and cuboid bones, comparing the fixation of the tendon to the bone using bone anchors and bone tunnels. Twenty-six specimens were tested for ultimate load to failure comparing Mitek Superanchor fixation with no. 1 and no. 5 braided polyethelyne suture to bone tunnel fixation. Mitek Superanchor with no. 5 suture failed at 223 N, compared with Mitek Superanchor with no. 1 suture at 134 N and bone tunnel at 143 N (P = 0.033). Mitek with no. 1 suture versus bone tunnel was not significantly different. The Mitek with no. 5 suture failed at the tendon/suture interface (75%), the Mitek with no. 1 suture failed at the suture/anchor interface (56%), and bone tunnel fixation failed most commonly by fracture of the tunnel (76%). This study is the first biomechanical analysis of the pullout strengths of bone tunnels or suture anchors in the cuboid bone. We have shown that the suture anchor has a pullout strength comparable or superior to a conventional bone tunnel in an in vitro situation. We believe it is a viable alternative to fixation of the tibialis anterior tendon to the cuboid when there is insufficient tendon length or failure of the bone tunnel.

Adult↗
PubMed2006

Bone density and bone area in Canadian Aboriginal women: the First Nations Bone Health Study.

INTRODUCTION: Canadian Aboriginal women are at increased risk of fracture compared with the general population. HYPOTHESIS: There is disproportionately reduced bone density in Aboriginal women as compared to white females of similar age. METHODS: A random age-stratified (25-39, 40-59 and 60-75) sample of Aboriginal women (n=258) and white women (n=181) was recruited. All subjects had calcaneus and distal forearm bone density measurements, and urban participants (n=397 [90.4%]) also had measurements of the lumbar spine, hip and total body. RESULTS: Unadjusted measurements were similar in the two groups apart from the distal forearm which showed a significantly lower mean Z-score in the Aboriginal women (p=0.03). Aboriginal women were heavier than white women (81.0+/-18.0 kg vs. 76.0+/-18.0 kg, p=0.02). Weight was directly associated with BMD at all measurement sites (p<0.00001) and potentially confounded the assessment of ethnicity on bone mass measurements. Weight-adjusted ANCOVA models demonstrated significantly lower bone density in Aboriginal than white women for the calcaneus, distal forearm, and total body (all p<0.05), but not at the other sites. ANCOVA models (adjusted for age, height and weight) were used to explore differences in bone area and bone mineral content (BMC). There was a significant effect of ethnicity on bone area with Aboriginal women having larger adjusted mean values than white women (lumbar spine p=0.038, total hip p=0.0004, total body p=0.020). In contrast, there was no detectable effect of ethnicity on BMC (all p>0.2). CONCLUSIONS: We identified significant site-specific differences in age-and weight-adjusted bone density for Aboriginal and white women. Larger bone area, rather than a reduction in BMC, appeared to be primarily responsible. Further work is needed to define how these differences in bone density and geometry affect indices of bone strength.

Adult↗
PubMed1997

Serum bone alkaline phosphatase is superior to plasma levels of bone matrix proteins for assessment of bone metabolism in patients receiving renal transplants.

The plasma concentrations of two bone matrix proteins (osteocalcin, osteonectin) were monitored in 56 samples from 14 patients receiving renal transplants and the values compared with serum bone alkaline phosphatase mass concentrations and osteotropic hormone levels (parathyroid hormone, calcitriol). There were no significant changes in the concentrations of plasma osteonectin at any time after transplantation, as compared with the values before transplantation (P > 0.1). None of the plasma samples showed osteonectin levels above the reference interval. There was a weak but significant relationship between platelet counts and plasma osteonectin levels (r = +0.322; P < 0.05). Osteocalcin showed a marked decrease of the values 1 week following transplantation as compared with the values before transplantation without further change of the values 1 and 3 months after transplantation (P > 0.5) whereas 3 months after transplantation bone alkaline phosphatase levels were higher than before transplantation (P < 0.05). Multiple regression analysis (performed with data from 42 samples obtained after transplantation) revealed serum creatinine as an independent predictor of plasma osteocalcin whereas serum calcitriol was an independent predictor of serum bone alkaline phosphatase (P < 0.05). No correlation was observed between serum calcitriol/plasma parathyroid hormone on the one hand and plasma osteocalcin on the other (P > 0.05). After transplantation there was a lack of correlation between serum bone alkaline phosphatase mass concentrations and plasma osteocalcin values (P > 0.05). In conclusion, serum bone alkaline phosphatase should be preferred to bone matrix proteins for the assessment of bone metabolism in patients receiving renal transplants: (a) bone alkaline phosphatase-but not osteocalcin-is significantly correlated with calcitriol and adequately reflects increased bone formation after renal transplantation; (b) interpretation of osteocalcin values is severely hampered by their strong correlation with serum creatinine concentrations; (c) plasma osteonectin determinations are not useful for monitoring bone formation.

Adult↗
PubMed1997

Comparison of alveolar bone loss, alveolar bone density and second metacarpal bone density, salivary and gingival crevicular fluid interleukin-6 concentrations in healthy premenopausal and postmenopausal women on estrogen therapy.

BACKGROUND: Osteoporosis is an age-related metabolic bone disease characterized by decreased mass and increased susceptibility to fracture. The literature suggests a relationship between oral bone loss and skeletal osteoporosis; however, most studies have produced conflicting results. The purpose of this study was to determine if a relationship exists among alveolar bone loss, alveolar bone density, second metacarpal density, salivary and gingival crevicular fluid interleukin 6 (IL-6), and IL-8 concentrations in premenopausal and postmenopausal healthy women receiving estrogen therapy. METHODS: Twenty-eight healthy women (aged 23-78) were evaluated for this study. A vertical bitewing and hand radiographs were taken, and the subjects were evaluated for the presence of active periodontitis. The bitewing and hand radiographs were digitized, and measurements were made from the cemento-enamel junction to the alveolar crest from both arches. Bone density was evaluated in the maxillary and mandibular alveolar process and at the mid-shaft of the second metacarpal. Percent cortical area and the moment of inertia measurements were also determined. Stimulated whole saliva was collected for a 5-min period using a cube of paraffin as a stimulant and was analyzed for total protein by a colorimetric reaction and IL-6 and IL-8 by ELISA. RESULTS: The results of the study showed that postmenopausal women on estrogen therapy had more alveolar bone loss, more missing teeth, and reduced alveolar and second metacarpal bone density than premenopausal women. In addition, postmenopausal women on estrogen therapy had higher salivary IL-6 concentrations than premenopausal women. Alveolar bone densities were also strongly correlated to second metacarpal densities. CONCLUSIONS: The results of the study suggest that changes in alveolar bone density and levels of bone resorptive cytokines in saliva may be secondary to changes in menopausal status. These changes may predispose loss of alveolar bone with resultant loss of teeth.

Adult↗
PubMed2005

Cemented cup stability during lever-out testing after acetabular bone impaction grafting with bone graft substitutes mixes containing morselized cancellous bone and tricalcium phosphate--hydroxyapatite granules.

Bone defects after failed total hip arthroplasty can be reconstructed with impacted morselized bone grafts and a cemented cup. In the near future the amount of bone grafts available for surgical purposes will be insufficient. Ceramic calcium phosphates [tricalcium phosphate (TCP) and hydroxyapatite (HA)] have been widely considered as potential bone graft substitutes or bone graft extenders. In the past, mechanical experiments have been performed to determine implant stability of bone grafts and ceramic TCP-HA granules mixes under a compressive load. However, in-vivo migration studies suggest that shear loading may be equally important. This in-vitro study investigated the initial stability of cups reconstructed with various mixes of bone grafts and ceramic TCP-HA granules in a lever-out situation, where shearing is the predominant loading mode. It was found that the cups reconstructed with mixes of bone graft and TCP-HA granules exhibited greater mechanical stability than the cups reconstructed with bone grafts only. It is concluded that from a mechanical standpoint, when considering shear force resistance, 50-50 per cent volume mix and 25-75 per cent volume mix of morselized cancellous bone graft and TCP-HA granules both provide adequate initial cup stability and can be used for acetabular reconstructions with the bone impaction grafting technique.

Acetabulum↗
PubMedDate not supplied

Bone healing following the use of hydroxyapatite or ionomeric bone substitutes alone or combined with a guided bone regeneration technique: an animal study.

The healing of standardized bone defects grafted with either particulate ionomeric or hydroxyapatite bone substitutes was compared in the mandibular ramus of 30 Sprague-Dawley rats. The possible additional response achieved when combining these materials with a guided bone regeneration (GBR) technique was also evaluated. Three groups of 10 animals received either no implant material or ionomeric or hydroxyapatite bone substitute in defects in the right ramus. The left mandibular defects received the same treatment, except that the operation site was covered by a membrane (GBR technique). Half of the animals were sacrificed at 4 and 10 weeks following surgery, and the inflammatory response at the implant site and the amount of new bone formed in the defects were determined histomorphometrically. Defects implanted with ionomeric bone substitute exhibited more bone formation (4 weeks = 3.19 +/- 0.35 mm2, 10 weeks = 5.35 +/- 0.26 mm2) than both defects that received no treatment (4 weeks = 0.88 +/- 0.35 mm2, 10 weeks = 2.1 +/- 0.49 mm2), membrane alone (4 weeks = 1.21 +/- 0.05 mm2) or hydroxyapatite bone substitute (4 weeks = 1.41 +/- 0.46 mm2, 10 weeks = 3.34 +/- 0.41 mm2) at 4 weeks (P < or = .01) and at 10 weeks (P < or = .05). The use of a GBR technique did not increase the amount of bone formed, compared to the use of bone substitutes alone. Hydroxyapatite and ionomeric bone substitutes used alone were more effective in inducing repair of the defects than was GBR membrane alone. The use of hydroxyapatite was associated with a greater inflammatory reaction (P < or = .01) than was ionomer in this model.

Analysis of Variance↗
PubMed2002

The effect of intravenous pamidronate on bone mineral density, bone histomorphometry, and parameters of bone turnover in adults with type IA osteogenesis imperfecta.

The type IA osteogenesis imperfecta (OI) phenotype is characterized by multiple fractures, blue sclerae, and minimal skeletal deformity without dentinogenesis imperfecta. The object of this study was to determine the effect of treatment with intravenous pamidronate (30 mg) every 3 months on bone density and bone histomorphometry in adults with type IA OI. After an initial iliac crest bone biopsy eight subjects, 5 women and 3 men, entered a treatment program lasting 21-30 months. Five subjects, all women, completed the study which included a posttreatment iliac crest bone biopsy. Pamidronate treatment led to significant increases in bone mineral density (BMD), measured by DXA, in the lumbar spine at 12 months (P = 0.05) and in the femur neck (P = 0.02) at 24 months. Significant increases in BMD were also seen in femoral trochanter at 12 months (P = 0.05) and at 24 months (P = 0.02), and in Ward's triangle at 12 months (P = 0.02) and 24 months (P = 0.05). Mean osteocalcin levels decreased 32%, C-terminal procollagen peptide and bone alkaline phosphatase declined 12% and 47% at 15 and 21 months, respectively. Deoxypyridinoline crosslink excretion decreased 31%. Posttreatment bone biopsy revealed a significant 6.3% increase in mean bone trabecular volume (P = 0.01). Mean cortical thickness increased from 848 mm to 1384 mm (P = 0.01) and cortical porosity decreased 13.2% (P = 0.01). Bone formation rate increased significantly in all 5 patients from 6.6 to 15.3 mm2/yr (P = 0.01). Mineral apposition rate was unchanged. These results indicate that intravenous pamidronate, 30 mg every 3 months, may have significant effects on bone density and histomorphometry in adults with type IA OI. Responses at higher doses remain to be evaluated.

Adult↗
PubMed1997

Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and parathyroid ultrasound in comparison with bone histology.

Bone biopsies were studied in 73 patients to determine if a two-site radioimmunometric assay for serum bone alkaline phosphatase (BAP), total serum alkaline phosphatase (ALP), serum intact parathyroid hormone (iPTH), hand X-rays, regional bone mineral density (BMD) measurements and parathyroid enlargement detected by ultrasonography could accurately predict renal osteodystrophy. In the patients studied 57 had hyperparathyroid bone disease, 4 mixed renal osteodystrophy, 3 adynamic bone disease, 1 osteomalacia and 8 normal histology. Serum BAP, ALP and iPTH correlated positively with mineral apposition rate, osteoblastic, osteoid and eroded surface. In the diagnosis of hyperparathyroid bone disease serum iPTH was the most sensitive investigation, detecting 81% of patients at a level > 100 pg/ml but with a specificity of only 66%. Serum BAP was more sensitive, 70% at a level of > 10 ng/ml, than serum total ALP, 30% at a level of 300 IU/l, with similar specificities, 92 and 100%, respectively. Ultrasound detection of an enlarged parathyroid gland had a sensitivity of 64% and a specificity of 100% for the diagnosis of hyperparathyroid bone disease. Hand X-rays had a poor sensitivity, 47%, but a high specificity, 92%, for the detection of hyperparathyroid bone disease. The majority of patients had regional BMD values within the normal reference range and this test was of poor discriminatory value. The non-invasive markers were unable to distinguish between patients with low turnover, mild hyperparathyroidism and patients with normal histology. In conclusion the measurement of serum iPTH is a useful screening tool for the detection of hyperparathyroid bone disease which can be confirmed by the finding of a raised serum BAP or parathyroid enlargement. For definitive diagnosis, however, the gold standard remains bone biopsy and at present one cannot recommend any non-invasive method as an adequate substitute.

Adult↗
PubMedDate not supplied

Effects of hyperthermia on bone. II. Heating of bone in vivo and stimulation of bone growth.

Previous studies in vitro have shown that it is possible to achieve comparable temperature distribution in bone and the adjacent soft tissues, under appropriate experimental conditions. The objective of the present work was to determine the effects of hyperthermia on bone in vivo. In order to obtain direct temperature measurements in bone, catheters were surgically installed on top of and inside the medullary cavity of the femur of normal rabbits. The thighs were irradiated with 915 MHz microwaves for 45 min, once or twice a week. The temperatures on and inside the bone were maintained between 42.5 and 44.0 degrees C; the resulting temperatures in the muscle were within 1.0 degrees C at depths equidistant from the applicator. After four to six treatments the femora were excised for histopathological examination. New trabecular bone was deposited around the catheters; most bone components including periosteum, osteoid, and fully calcified matrix could be seen. Large numbers of osteoblasts and osteoclasts lined the trabecular surfaces, and numerous cement lines were visible, running in all directions, indicating extensive bone deposition and remodelling. In contrast, control bones (catheters installed--no hyperthermia) showed much less ossification, with many areas of thin incomplete osteoid. Further, bones treated with hyperthermia only (no surgical trauma) showed no such changes. Thus, it appears that following an initial insult, hyperthermia promotes bone deposition.

Animals↗
PubMedDate not supplied

Bone-forming and bone-resorbing cell lines derived from bone marrow in tissue culture.

The differentiation of connective tissue outgrowths of adult bone marrow in response to the organic matrix of bone was observed in tissue culture by correlated histologic, electron microscopic, biochemical, and radioisotope-labeling methods. On a substratum of bone matrix gelatin, myelogenous cells degenerate and disappear while stromal and perivascular cells proliferate and differentiate into mesenchymal-type, monocytoid, and giant cells. From primary cultures of bone marrow cells on bone matrix, cartilage differentiates in isolated areas but only in small islets. With continuous subculture through 25 generations, the proportions of two functionally different populations of chondrogenetic and matrix-resorbing cells gradually emerge. Up to the time of the ninth generation of subculture, the chondrogenetic population predominates. After the 14th to the 25th generation, clones of matrix-resorbing large monocytoid cells predominate and rapidly digest the matrix substratum. Measurements of 35S uptake demonstrate that control cultures of muscle-derived mesenchymal-type cells produce about twice as much cartilage as marrow-derived mesenchymal-type cells. A decline in the chondrogenetic cell population and corresponding rise in the matrix-resorbing cell population is demonstrable by a progressive increase in the quantity of hydroxyproline-containing peptides in the culture medium. This decline is not attributable to conditions in culture because there was progressive loss of chondrogenetic activity of the eighth and 20th passage even when the cells were transplanted in diffusion chambers back into an isologous host. The problem is how to account for the competence of marrow stromal cells to differentiate into bone without bone matrix in vivo but not in vitro. Mixed cultures of muscle and marrow outgrowths produce only half as much cartilage (measured by 36S-uptake/microgramDNA in the system) as muscle outgrowths alone. These observations suggest that a bone marrow-derived matrix-resorbing cell population, by some unknown mechanism, inhibits proliferation of cartilage-bone precursor cell populations. The nature of the inhibition requires investigation by detailed biochemical analyses of marrow cell culture media and chemical extracts of whole bone marrow tissue.

Adult↗