Bone Mineralization Rate Research Articles

Malfunction of bone marrow-derived osteoclasts and the delay of bone fracture healing in diabetic mice

It is well known that bone fracture healing is delayed in diabetes mellitus, but the mechanism remains to be elucidated. Since several studies have demonstrated that diabetes causes abnormalities in bone marrow-derived cells, we used the streptozotocin (STZ)-induced diabetic mouse model after bone marrow transfer from green fluorescent protein (GFP) transgenic mice, and examined fracture healing. Compared with nondiabetic mice, diabetic mice at 3 weeks after fracture showed a decrease in mineralized callus, with the remainder consisting of cartilage. Bone formation parameters and mineralization rate were not altered in the STZ mice, but bone resorption parameters were significantly decreased. Therefore, the delayed bone formation in the STZ mice may have resulted from an impairment of cartilage resorption. Interestingly, we found that 80% of the osteoclasts in the callus were derived from bone marrow and the sizes of the osteoclasts as well as the resorption pits formed were significantly smaller in the diabetic mice. Moreover, transcript analysis using RNA isolated by laser capture microdissection (LCM) showed that the expression of DC-STAMP, a putative pivotal gene for osteoclast fusion, was decreased in osteoclasts from diabetic mice. Since the sustainability of osteoclast function depends on the controlled renewal of multinuclear osteoclasts, impaired osteoclast function in diabetes may contribute to decreased cartilage resorption and delayed endochondral ossification.

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

The capacity for bone healing reportedly is limited in osteoporosis with a less than ideal environment for healing of bone grafts. We therefore developed a composite bone substitute with rhBMP-2 loaded gelatin microsphere (GM) and calcium phosphate cement (CPC) to use in osteoporosis. We asked whether (1) controlled release of rhBMP-2 could be improved in this composite bone substitute and (2) increasing factors released from the bone substitute could accelerate osteoporotic bone healing. We soaked rhBMP-2/GM/CPC and rhBMP-2/CPC composites in simulated body fluid for 28 days and then determined the amount of rhBMP-2 released. Both composites were implanted in bone defects of osteoporotic goats and left in place for 45 and 140 days; the specimens then were evaluated mechanically (pushout test) and morphologically (CT scanning, histology). The in vitro study showed the new composite released more rhBMP-2 compared with rhBMP-2/CPC. CT showed the defects healed more quickly with new grafts. The bone mineralization rate was greater in rhBMP-2/GM/CPC than in rhBMP-2/CPC after 45 days of implantation and the pushout test was stronger after 45 and 140 days of implantation. The new graft composite released more loaded factors and appeared to repair osteoporotic bone defects. These preliminary data suggest the new composite can be used as a bone substitute to accelerate healing of fractures and bone defects in osteoporosis.

Cross-calibration of 45calcium kinetics against dynamic histomorphometry in a rat model to determine bone turnover

Techniques for assessing bone dynamic are in high demand. Calcium (Ca) kinetic studies are currently being used in our clinical studies of bone turnover in adolescents and elderly. The technique has rarely been compared to the standard method of bone dynamic histomorphometry. We perturbed bone turnover through ovariectomy and sub-optimal dietary Ca in a female rat model to cross-calibrate Ca kinetics against dynamic histomorphometry. Kinetic studies involved oral and intravenous administration of 45Ca and monitoring the tracer in blood, urine, feces, and bone over a 3-day period as part of a metabolic Ca balance study. Histomorphometric indices of mineral apposition rate, mineralizing surface, and bone formation rate were obtained from proximal metaphysis and mid-diaphysis region of tibial bone. Bone mineralization and resorption rates at the whole skeletal level as evaluated by kinetic studies were significantly correlated with the volume-based bone formation rate (BFR/BV) evaluated by dynamic histomorphometry in metaphyseal trabecular bone (r=0.72 and r=0.61, respectively, p<0.001) and surface-based bone formation rate (BFR/BS) in tibial cortex (r=0.63, p<0.001 and r=0.59, p<0.01, respectively). Significant correlations were also demonstrated between bone resorption and mineralization rates at the whole skeletal level (r=0.91, p<0.001) using 45Ca kinetic data. Ca kinetic modeling showed an increase (p<0.001) in skeletal resorption and formation rates in response to ovariectomy (27.6 vs. 13.8mg/d for bone resorption and 42.7 vs. 28mg/d for bone formation in ovariectomized vs. their Sham-operated control animals, respectively). Ca kinetic data also showed that bone formation decreased by 30% and whole bone balance by 50%, when dietary Ca level was reduced from 0.4% to 0.2% (34.2 vs. 23.8mg/d and 10.4 vs. 5.1mg/d, respectively, p<0.001). Our data suggest that Ca kinetic studies can be used reliably to rapidly detect changes in bone turnover at the whole skeletal level in response to interventions.

Determinants of peak bone mass and bone mineralization rates in 470 healthy children, adolescents and young adults: A prospective study

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Biomechanical performance of diaphyseal shafts and bone tissue of femurs from hypothyroid rats

The bone changes in hypothyroidism are characterized by a low bone turnover with a reduced osteoid apposition and bone mineralization rate, and a decreased osteoclastic resorption in cortical bone. These changes could affect the mechanical performance of bone. The evaluation of such changes was the object of the present investigation. Hypothyroidism was induced in female rats aged 21 days through administration of propylthiouracil in the drinking water for 70 days (HT group). Controls were untreated rats (C group). Right femur mechanical properties were tested in 3-point bending. Structural (load bearing capacity and stiffness), geometric (cross-sectional area and moment of inertia) and material (modulus of elasticity) properties were evaluated. The left femur was ashed for calcium content determination. Plasma T(4) concentration was significantly decreased in HT rats. Body and femur weight and length in HT rats were also reduced. Femoral calcium concentration in ash was higher in HT than in C rats. However, the femoral calcium mass was significantly lower in HT than in C rats because of the reduced femoral size seen in the former. The stiffness of bone material was higher in HT than in C rats, while the bone geometric properties were significantly lower. The "load capacity" was between 30 and 50% reduced in the HT group, although, the differences disappeared when the values were normalized per 100-g body weight. The lowered biomechanical ability observed in the femoral shafts of HT rats seems to be the expression of a diminished rate of growth. Qualitative alterations in the intrinsic mechanical properties of bone tissue were observed in HT rats, probably because the mineral content and the modulus of elasticity were positively affected. The cortical bone of the HT rat thus appears as a bone with a higher than normal strength and stiffness relative to body weight, probably due to improvement of bone material quality due to an increased matrix calcification.

Restoration of segmental bone defect by calcium sulfate pellet: experiment with rabbit

To compare the effects of different calcium sulfate pellets made by different methods in treating segmental defect of bone. Eighty New Zealand white rabbits underwent cutting off a segment in the middle part of radius so as to establish models of radial segmental defect, and than were divided into 4 groups: Group A as control group, Group B with calcium sulfate pellet made by routine method implanted into the defect, Group C with chitosan coated pressed calcium sulfate pellet implanted into the defect, and Group D with chitosan coated pressed calcium sulfate pellet combined with recombinant human bone morphogenetic protein (rhBMP)-2 implanted into the defect: X-ray photography was done every 4 weeks to observe the new bone formation. Four, 8, and 12 weeks 5 rabbits from each group were killed. The defect segments with parts of normal bone at both ends were cut off to undergo fluorescence microscopy and biomechanic three point bending test. X-ray photography and histological examination showed that new bone formation of cortex and reconstruction of marrow cavity were seen in Groups D and C, especially in Group D. The new bone mineralization rate of Group D was significantly higher than that of Group C (P<0.05) which was significantly higher than that of Group B (P<0.01). The anti-bending strength ratio of Group D was (47.5%+/-2.1%, significantly higher than that of Group C [(39.6+/-1.7)%, F=125.3, P<0.01], and the anti-bending strength ratios of Groups D and C were both significantly higher than those of Groups B and A [(23.6+/-3.3)% and (21.3+/-2.7)%]. Chitosan coated pressed calcium sulfate pellet shows relatively higher anti-bending strength and slightly slower resorption that closely coincide with the growth rate of new bone. It can be used to restore segmental bone defect, and particularly when combined with rhBMP-2.

Calcium and vitamin D and bone strength ‐ Scientific substantiation of a health claim related to calcium and vitamin D and bone strength pursuant to Article 14 of Regulation (EC) No 1924/2006 ‐ Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies

Calcium and vitamin D and bone strength ‐ Scientific substantiation of a health claim related to calcium and vitamin D and bone strength pursuant to Article 14 of Regulation (EC) No 1924/2006 ‐ Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies

On the role of bone damage in calcium homeostasis

Bone serves as the reservoir of some minerals including calcium. If calcium is needed anywhere in the body, it can be removed from the bone matrix by resorption and put back into the blood flow. During bone remodelling the resorbed tissue is replaced by osteoid which gets mineralized very slowly. Then, calcium homeostasis is controlled by bone remodelling, among other processes: the more intense is the remodelling activity, the lower is the mineral content of bone matrix. Bone remodelling is initiated by the presence of microstructural damage. Some experimental evidences show that the fatigue properties of bone are degraded and more microdamage is accumulated due to the external load as the mineral content increases. That damage initiates bone remodelling and the mineral content is so reduced. Therefore, this process prevents the mineral content of bone matrix to reach very high (non-physiological) values. A bone remodelling model has been used to simulate this regulatory process. In this model, damage is an initiation factor for bone remodelling and is estimated through a fatigue algorithm, depending on the macroscopic strain level. Mineral content depends on bone remodelling and mineralization rate. Finally, the bone fatigue properties are defined as dependent on the mineral content, closing the interconnection between damage and mineral content. The remodelling model was applied to a simplified example consisting of a bar under tension with an initially heterogeneous mineral distribution. Considering the fatigue properties as dependent on the mineral content, the mineral distribution tends to be homogeneous with an ash fraction within the physiological range. If such dependance is not considered and fatigue properties are assumed constant, the homogenization is not always achieved and the mineral content may rise up to high non-physiological values. Thus, the interconnection between mineral content and fatigue properties is essential for the maintenance of bone's structural integrity as well as for the calcium homeostasis.

The Rate of Bone Mineralization in Birds Is Directly Related to Alkaline Phosphatase Activity

Recent studies have suggested that a biochemical marker, plasma alkaline phosphatase (ALP), can be used as a general indicator of skeletal development in vertebrate animals. In birds, age-related variation in ALP activity, presumably due to bone formation processes, has been demonstrated, but to date, a direct connection between bone mineralization and enzyme activity has been elusive. In this study, we show that the activity of a bone isoform of ALP (bone ALP) is closely related to the overall rate of skeletal mineralization in nestlings of a small passerine bird, the great tit (Parus major L). Moreover, bone ALP activity predicted the rate of mineralization of leg and wing bones but not that of the skull. Liver isoform of ALP was only marginally related to the overall rate of skeletal mineralization, while no association with the mineralization of long bones was found. We conclude that bone ALP activity in the blood plasma is a reliable biomarker for skeletal mineralization in birds. This marker enables detection of subtle developmental differences between chicks of similar structural size, potentially facilitating the prediction of offspring mid- and long-term survival.

A novel multiphase anodic spark deposition coating for the improvement of orthopedic implant osseointegration: An experimental study in cortical bone of sheep

The effect of a new three-step anodic spark deposition process, labeled TiSpark, including two consecutive treatments performed first in a P solution and second in Ca solution, followed by an additional alkali etching step, was investigated for the improvement of osseointegration of commercial grade 2 titanium, machined (Ti) or Al(2)O(3) sandblasted (Ti-SA), cylindrical implants (12 mm in length and 4 mm in diameter) in cortical bone of 12 adult sheep. Histomorphometric and microhardness measurements were carried out at each experimental time (4, 8, and 12 weeks) to quantify the bone-to-implant contact around the implants as well as the newly bone hardness and bone maturation index. TiSpark treated surfaces were covered by a thick layer of crystalline anatase TiO(2) and by a further Ca/P layer. Bone tissue extends and grows on the surface of the TiSpark treated implants without any fibrous tissue, enhancing the short-term osseointegration properties of implant. Bone mineralization rate was also influenced by the chemical composition of implants and sandblasted materials presented the lowest bone maturation rate at the interface. Data suggests that the TiSpark treatment produces a modification of the Ti surface, which presents good bioactivity and may be suitable for achieving a stable implant osseointegration.

Regulation of mineral-to-matrix ratio of lumbar trabecular bone in ovariectomized rats treated with risedronate in combination with or without vitamin K2.

The relationship between bone turnover and bone tissue and material properties was examined in ovariectomized (OVX) rats treated with risedronate in combination with or without vitamin K2. Seventy female rats, 18 weeks of age, were assigned to 7 groups (n=10): sham-operated + vehicle control; OVX + vehicle control; OVX + risedronate 0.1, 0.5, or 2.5 mg/kg/day po; OVX + vitamin K2 approximately 30 mg/kg/day po; OVX + vitamin K2 (approximately 30 mg/kg/day) and risedronate (0.5 mg/kg/day). Treatments were given daily for 9 months. To assess bone turnover, we measured serum osteocalcin and urinary deoxypyridinoline at 0, 3, and 9 months. To assess vertebral and femoral tissue and material properties, bone mass, bone mineral density (BMD by DXA), trabecular bone structure (vertebra: 3D-microCT), cortical bone structure (femur: histomorphometry), biomechanical properties, and mineral properties (mineral-to-matrix and carbonate-to-phosphate ratios by Fourier transform infrared microspectroscopy) were measured ex vivo at 9 months. Ovariectomy increased bone turnover and induced significant loss of bone mass/density, structure, mineral properties (mineral-to-matrix ratio), and strength. Risedronate produced dose-dependent inhibition of the ovariectomy-induced increase in turnover and loss of bone mass/density, structure, mineral-to-matrix ratio, and strength, with a lowest effective dose of 0.1-0.5 mg/kg/day. High-dose risedronate (2.5 mg/kg/day) did not induce increases in any parameter above that of sham control. Vitamin K2 had no effects. In the OVX groups, urinary deoxypyridinoline at 3 and 9 months correlated significantly with vertebral BMD, trabecular bone volume, ultimate load, stiffness, and mineral-to-matrix ratio, and with femoral BMD, cortical area, and ultimate load. These results support the concept that changes in bone tissue and material properties can result directly from changes in bone turnover. Different effects among different drugs on material properties, including mineral-to-matrix ratio, may reflect differences in the relative rate and magnitude of osteoclastic bone resorption and osteoblastic primary bone mineralization.

Calcitonin administration in a rabbit distraction osteogenesis model.

The effect of salmon calcitonin on the maturation of the regenerate bone was assessed in an experimental model in rabbits. Twenty-six New Zealand White male rabbits, approximately 5 months old and weighing 3 to 3.5 kg, were subjected to a mid-diaphyseal tibial osteotomy. After 5 days, the right tibia was lengthened gradually at a rate of 0.375 mm every 12 hours, for 10 days. Ten international units of salmon calcitonin were administered daily subcutaneously to the study group (14 animals), whereas the animals of the control group (12 animals) were injected with a placebo, for the duration of the experiment. The bone mineral density of the regenerate bone was assessed on Days 20, 35, 45, and 55 of the experiment, in both groups, using dual energy xray absorptiometry. No statistical significant difference was found in the dual energy xray absorptiometry measurements between the study and control groups regarding the change of the bone mineral density of the new bone relative to a preoperative baseline measurement. Characteristic time-related changes were observed in the bone mineral density of the regenerate bone during its maturation, which proved to be identical in both groups. It seems that the administration of calcitonin does not enhance regenerate bone mineralization rate and tendency during bone lengthening.

Hypothalamic Y2 receptors regulate bone formation.

Neuropeptide Y (NPY) is a downstream modulator of leptin action, possibly at the level of the arcuate nucleus where NPY neurons are known to express both leptin receptors and Y2 receptors. In addition to the well-described role of NPY and leptin in energy balance and obesity, intracerebroventricular administration of NPY or leptin also causes bone loss. Here we show that Y2 receptor-deficient mice have a twofold increase in trabecular bone volume as well as greater trabecular number and thickness compared with control mice. We also demonstrate that central Y2 receptors are crucial for this process, since selective deletion of hypothalamic Y2 receptors in mature conditional Y2 knockout mice results in an identical increase in trabecular bone volume within 5 weeks. This hypothalamus-specific Y2 receptor deletion stimulates osteoblast activity and increases the rate of bone mineralization and formation, with no effect on osteoblast or osteoclast surface measurements. The lack of any changes in plasma total calcium, leptinemia, or hypothalamo-pituitary-corticotropic, -thyrotropic, -somatotropic, or -gonadotropic output suggests that Y2 receptors do not modulate bone formation by humoral mechanisms, and that alteration of autonomic function through hypothalamic Y2 receptors may play a key role in a major central regulatory circuit of bone formation.

Growth, bone mineralization, and heat and low oxygen tolerance in European whitefish ( Coregonus lavaretus L.) fed with graded levels of phosphorus

Trials were conducted to determine the dietary phosphorus (P) requirement of European whitefish, and to assess the effects of sub-optimal P feeding on growth, bone mineralization, lipid accumulation in the body and on heat and low-oxygen tolerance. Four replicate groups of whitefish fingerlings were fed in excess with one of five semipurified diets containing 4.4 to 14.9 g P kg −1. The P requirement was estimated by nonlinear curve fitting to bone mineralization and growth rate data. Dietary P and energy availabilities were measured at the determined requirement level. Fish fed no P supplement showed typical hypophosphatemia in poorly mineralized bones, a low whole-body P content and a low plasma phosphate concentration. Hypophosphatemic fish grew slower and had elevated whole body lipid concentrations. To obtain 95% of the maximum vertebra ash concentration and maximum growth, respectively, 6.5- and 6.2-g available P kg −1 diet was required. Fish fed low dietary P contents had higher whole body lipid levels than fish fed P at or above the determined requirement level. Hypophosphatemic fish had slightly, although statistically significant, lower upper lethal temperature than fish fed with adequate P contents (28.8 vs. 29.4 °C). Tolerance of low dissolved oxygen did not differ between fish fed low or high P contents (1.47 vs. 1.45 mg l −1).

Characterization of biomaterials used for bone regeneration by FTIR spectroscopy

FTIR spectroscopy has been used to analyse the process of bone regeneration taking place in the presence of surface modified carbon materials. Two types of carbon implant materials differing in their surface properties have been examined: an oxidized carbon fabric and a carbon fabric coated with a pyrolytic carbon layer. Samples of bone tissue have been retrieved at different times after implantation for spectroscopic study. The ratio of bone components has been calculated from the FTIR spectra of the samples, based on the integrated areas of the bands brought about by the vibrations of phosphates and amide groups. Additionally, the analysis of the shape and intensity of these bands provided information on developing and on the rate of bone mineralization. The investigation has shown that healing is faster in the presence of the carbon fabric coated with a pyrolytic carbon layer used as an implant material.

Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta

Preclinical models have shown that transplantation of marrow mesenchymal cells has the potential to correct inherited disorders of bone, cartilage, and muscle. The report describes clinical responses of the first children to undergo allogeneic bone marrow transplantation (BMT) for severe osteogenesis imperfecta (OI), a genetic disorder characterized by defective type I collagen, osteopenia, bone fragility, severe bony deformities, and growth retardation. Five children with severe OI were enrolled in a study of BMT from human leukocyte antigen (HLA)-compatible sibling donors. Linear growth, bone mineralization, and fracture rate were taken as measures of treatment response. The 3 children with documented donor osteoblast engraftment had a median 7.5-cm increase in body length (range, 6.5-8.0 cm) 6 months after transplantation compared with 1.25 cm (range, 1.0-1.5 cm) for age-matched control patients. These patients gained 21.0 to 65.3 g total body bone mineral content by 3 months after treatment or 45% to 77% of their baseline values. With extended follow-up, the patients' growth rates either slowed or reached a plateau phase. Bone mineral content continued to increase at a rate similar to that for weight-matched healthy children, even as growth rates declined. These results suggest that BMT from HLA-compatible donors may benefit children with severe OI. Further studies are needed to determine the full potential of this strategy.

Clinical Research: Assessment, Prevention and Management of Metabolic Bone Disease in Very Low Birthweight Infants: The Role of the Neonatal Nutritionist

Very‐low‐birth‐weight (VLBW) preterm infants have an increased risk of developing metabolic bone disease (MBD) over term infants because of their decreased opportunity for intrauterine bone mineralization. Neonatal nutritionists are playing an increasingly important role in the prevention and management of MBD. The purpose of this survey study was to assess their role in the assessment, prevention, and management of MBD in VLBW infants. A total of 49 neonatal nutritionists primarily working in Level III Newborn Intensive Care Units (NICU) were surveyed to determine their clinical practice in the assessment and management of MBD. A total of 83.7% of the respondents assessed skeletal health at an average of 2.3 weeks of life with 16.3% assessing within the first week of life. The majority (93.9%) used serum phosphorus and alkaline phosphatase values in skeletal health assessment. Neonatal nutritionists tended to underestimate the incidence of MBD in their NICUs, with 79.2% estimating the incidence to be 5% or less. Parenteral nutrition (PN) was initiated by days 0 to 3 of life by 95.9% of the respondents, whereas enteral nutrition (EN) was begun on day 4 to 7 by 55.1% of respondents or on days 0 to 3 of life by 28.6% of the respondents. Optimal goals for ratios of calcium to phosphorus were reported as 1.3 to 1.7: 1 for PN by 84.7% and 1.8 to 2:1 in EN by 73.8% of the NICU nutritionists. Enteral vitamin supplements were used routinely by 70.2% of the respondents, with 53.2% using a pediatric multivitamin. Neutra‐Phos (44.8%), providing phosphate, and Neo‐Calglucon (37.9%), which provides calcium gluconate, were the most commonly used mineral supplements. The neonatal nutritionists surveyed played an active role in educating members of the health care team. Respondents were primarily responsible for documenting recommendations in medical records and direct communication with the NICU team on rounds (98.0%). The most common educational activities the respondents performed included: developing and revising PN order forms (77.1%), NICU handbook development (64.6%) and regular lectures to interns/residents (58.3%) and neonatologists (41.7%). The descriptive survey found that neonatal nutritionists played an increasingly proactive role in a variety of direct patient care activities, ie, risk assessment, initiation of early PN and EN, optimizing calcium and phosphorus intake and education of residents and NICU staff to promote optimal bone mineralization rates.

In vivo biocompatibility and mechanical study of novel bone-bioactive materials for prosthetic implantation.

Two epoxy materials with or without adhesively bonded hydroxyapatite (HA) coatings were studied for their biocompatibility and mechanical pushout strength using in vivo implantation in the rabbit lower femur for a duration of 10 days to 6 months. Both were two-part epoxies cured at room temperature for 24 h, with material 1 (Ampreg 26; SP Systems Limited, Cowes, UK) postcured at 110 degrees C (Tg approximately 80 degrees C) and Material 2 (CG5052; Ciba Geigy Limited, Cambridge, UK) at 125 degrees C (Tg approximately 120 degrees C). Implantation in dead rabbit bone was performed to provide mechanical baseline levels. Polymethylmethacrylate (PMMA) and conventionally HA-coated titanium alloy (Ti-6Al-4V) were used as control materials. In the biological study, different fluorescent dyes were used to label newly formed bone. After 6 weeks of implantation, results from mechanical pushout tests showed that the interfacial shear strength (ISS) values were significantly higher than for dead bones with each of the different implants (p < .01-.001). HA-coated material 2 showed a significantly higher ISS value than the uncoated material (p < .05) after 6 weeks' implantation. However, the ISS value for the uncoated material 2 was significantly higher than for PMMA controls (p < .05). No significant differences in the ISS values were shown between HA-coated materials 1 and 2 and Ti-6Al-4V on in vivo implantation for 6 weeks. Failure points of the pushout test from the three HA-coated materials were defined by scanning electron microscopy. Specimens implanted with both HA-coated epoxies were fractured within the HA-coatings or the bone, while with HA-coated Ti-6Al-4V cracked between the coating and metal implant. The percentage of bone in contact with the implant surface was obtained by image analysis which showed that there were no significant differences between different materials after short time implantation (up to 6 week). Long-term implantation of the HA-coated material 2 showed that the percentage of bone contact had increased from 52.8+/-1.1% (6 week) to 80.0+/-0.3% (3 months) (p < .01) and remained at 81.0+/-0.8% (6 months). Measurements of bone mineralization rate (BMR) showed that after 3 weeks of implantation, there were no significant differences between PMMA and uncoated materials 1 and 2. After 6 weeks, the BMRs in animals implanted with either HA-coated material 1 or 2 were significantly higher than with HA-coated Ti-6Al-4V (p < .05-.0001 in both cases), but with HA-coated material 2 was lower than with this material uncoated (p < .05-.001). No significant differences were found between the two HA-coated epoxy materials. In addition, there were always lower BMRs during the third week of implantation than other periods regardless of biomaterial implanted. The study indicated that the adhesively bonded HA-coated novel epoxy materials were superior to conventional plasma-sprayed Ti-6Al-4V implants with respect to both BMR and bone integration with the implant surfaces. Adhesively bonded HA-coated epoxy materials had similar ISS values to HA-coated Ti-6Al-4V, but the former failed within the bone and coating, while the latter showed splitting between coating and metal.

Calcitonin alters bone quality in beagle dogs.

Because of its antiresorptive properties, calcitonin is widely used to prevent and treat osteoporosis. A stimulatory effect of calcitonin on osteoblasts has also been reported; however, a recent histologic study points to a negative effect of calcitonin on mineralization of cancellous bone. The present experiment was performed to determine whether the observed histological signs of alterations in mineralization are also observed in cortical bone and whether this results in changes in mechanical properties, mineral densities, or mineral properties of canine bone. Sixteen female adult beagle dogs were randomly allocated to receive either human calcitonin at a dose of 0.25 mg/dog (50 IU, n = 8) or vehicle (mannitol, n = 8) every other day for 16 weeks. At the end of the study, the dogs were euthanized. Both tibiae, L1 and L5 vertebrae, and iliac crest bone samples were excised and defleshed. Torsional mechanical properties of tibial diaphyses and compressive strengths of vertebrae were measured. Bone mineral densities (BMD) of tibiae and vertebrae were measured by using dual-energy X-ray absorptiometry. Ultrastructural mineral characteristics of iliac crest bone were determined by gravimetry and Fourier transform infrared spectroscopy (FTIR). Bone histomorphometry was performed in the cortical envelope of the iliac crest. Tibiae from dogs treated with calcitonin withstood significantly less maximum torque until failure, required less torsional energy to reach the maximum torque, and had less torsional stiffness than the tibiae from dogs treated with vehicle (p < 0.05). Cancellous cores of vertebrae from calcitonin-treated dogs withstood less compressive mechanical loading than did vertebral cores from vehicle-treated animals (p < 0.05). Dogs treated with calcitonin had less BMD of both tibiae and vertebrae than vehicle-treated animals (p < 0.05). Bones from calcitonin-treated dogs had significantly less ash content, which correlated with the lower phosphate-to-amide I (detected by FTIR) and greater carbonate-to-phosphate ratios than did bones from vehicle-treated dogs (p < 0.05). Calcitonin-treated dogs exhibited a decrease in bone formation and mineralization rates and an increase in mineralization lag time. These results point to a negative effect of calcitonin on bone quality. These findings are intriguing and call for further studies addressing whether the observed abnormalities are transient or permanent.

Alcohol Consumption by Young Actively Growing Rats: A Histomorphometric Study of Cancellous Bone

Alcohol consumption by young actively growing rats has been previously demonstrated to decrease bone density. This study addresses the mechanism of alcohol action on the early phases of bone growth and development using histomorphometric techniques. Four-week-old, female Sprague-Dawley rats were divided into three groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin-substituted calories were supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Proximal tibiae, including epiphyseal growth plate, were removed for analysis after 2, 4, 6, or 8 weeks on the diets. Trabecular volume and number were greatly reduced in the alcohol-fed animals; however, bone formation rates and mineralization rates were normal. Epiphyseal growth rate and proliferation rate were essentially stopped in the alcohol-fed animals.