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PubMed1985

Mineral and matrix alterations in the bones of incisors-absent (ia/ia) osteopetrotic rats.

The bones of incisors-absent (ia/ia) osteopetrotic rats differ from those of their normal littermates (ia/+) in histologic and radiographic appearance and in mechanical properties. This study examined how the mineral and matrices of osteopetrotic metaphyses and calvaria differed from normal controls. Bones of 11-day-old and 52-day-old osteopetrotic animals had higher ash (mineral) contents that age-matched controls; osteopetrotic metaphyses had elevated hexosamine contents, indicative of the persistence of cartilage. Calcium acidic phospholipid phosphate complexes, involved in initiation of hydroxyapatite formation in vivo and in vitro, were significantly reduced in content in all osteopetrotic bones. These results suggest that in the osteopetrotic rat, where osteoclast activity is defective, new mineral formation is reduced and replaced by accretion of mineral on existing crystals. Fractionation of osteopetrotic bone particles by density centrifugation demonstrated that the osteopetrotic bone was much more mineralized than that of age-matched controls. X-ray diffraction analysis of the mineralized fractions indicated a lack of growth of mineral crystals during maturation of the osteopetrotic animals. The absence of remodeling was apparent from the elevated Ca:P ratios of the highly mineralized osteopetrotic bone fractions, and from the high hexosamine content of these dense fractions. These observations may explain some of the unusual mechanical properties of osteopetrotic bone.

Animals↗
PubMed1987

Osteochondroma induced by reflection of the perichondrial ring in young rat radii.

In order to investigate the effects of reflection of the perichondrial ring in osteochondroma formation, the perichondrial rings of the epiphyseal growth plates in 42 young rat radii were turned to the metaphyseal periosteum by means of blunt dissection. Seven days after surgery a small nest of chondrocytes appeared on the metaphyseal-diaphyseal bone surface at the level of the tip of the reflected perichondrial ring. From the 9th to the 15th days the histological pattern of the osteochondroma was established. The osteochondroma was not connected with the hypertrophic cartilage of the growth plate. During the third and fourth weeks the osteochondroma began to regress with the disappearance of the cartilage nest. During the development of the lesion the bone grew normally and the growth plate migrated distally while the lesion remained at its initial site. The growth plate zone devoid of perichondrial ring was covered by fibrous connective tissue and no removal of the perichondrial ring occurred. These results suggest that the origin of this osteochondroma is the perichondrial ring cells whose polarity has been surgically changed.

Animals↗
PubMed1989

Influence of testosterone and dihydrotestosterone on bone-matrix induced endochondral bone formation.

A bone matrix-induced endochondral bone development model has been used to study the effects of androgens on different stages of bone development in castrated young adult rats. Androgen treatment, especially with dihydrotestosterone (DHT) for 7 days, inhibited 35SO4 incorporation by the developing cartilage in the induced plaques. Castrated control animals maintained for 11 days after implantation of bone matrix showed significantly lower calcium levels in the induced implant than was observed earlier in the unoperated controls. DHT treatment for 11 days caused dramatic increases in levels of calcium in the implants. Testosterone had little effect. When androgen treatment was continued for 21 days, while levels of alkaline phosphatase in the implants were unaffected, levels of calcium in the implants were significantly higher than on day 11 for both castrated control and androgen-treated animals. Peak alkaline phosphatase activity (day 10) is known to precede peak calcium mineralizing activity (day 12) in this model and it is also known that calcium levels remain high thereafter. Evaluation of calcium and alkaline phosphatase levels in the proximal tibial metaphyses of castrated control and androgen-treated groups of animals showed no changes after 11 days treatment. Prolonged treatment (21 days) elevated the levels of alkaline phosphatase whereas no change was observed in calcium levels in the tibial metaphyses. These findings demonstrate that androgens stimulate mineralization and that DHT is more active when used for short periods of time and in early stages of bone development in matrix-induced implants.

Alkaline Phosphatase↗
PubMed1988

Effect of gallium on bone mineral properties.

Gallium nitrate is biologically active in blocking bone resorption in vitro as well as in vivo. Administration of gallium nitrate to growing rats results in a dose-dependent accumulation of low levels of gallium in bone that is associated with specific changes in the mineral properties of bone. To elucidate in greater detail the changes induced by gallium, the properties of whole and density-fractionated bone samples from control and gallium-treated rats were examined. These studies showed that short-term treatment with gallium nitrate caused an increase in bone calcium and phosphate content. Devitalized bone powder from the gallium-treated rats was less soluble in acetate buffer and less readily resorbed by monocytes. Density fractionation analyses demonstrated that the largest proportion (76% by weight) of powdered metaphyseal bone particles from rats had a density of less than 2.15 g/cc. Following short-term treatment (14 days) with gallium nitrate (45 mg/kg body weight), a significant increase in the relative proportion of more dense bone (greater than or equal to 2.15 g/cc) was observed (24% for the control vs. 39% for the gallium-treated rats, P less than 0.01). In the diaphyseal samples, the largest proportion (88% by weight) of the bone powder had a density of greater than or equal to 2.15 g/cc. After short-term treatment with gallium, a slight decrease in mean diaphyseal particle density was observed. Measurement of calcium accretion with 45Ca in the gallium-treated rats demonstrated increased specific activity in the metaphyseal bone samples, densities = 2.0, 2.1, 2.15, and 2.25 g/cc; the difference was significant only for the 2.25 g/cc fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Expression of type I, type II, and type X collagen genes during altered endochondral ossification in the femoral epiphysis of osteosclerotic (oc/oc) mice.

The osteosclerotic (oc/oc) mouse, a genetically distinct murine mutation that has a functional defect in its osteoclasts, also has rickets and shows an altered endochondral ossification in the epiphyseal growth plate. The disorder is morphologically characterized by an abnormal extension of hypertrophic cartilage at 10 days after birth, which is later (21 days after birth) incorporated into the metaphyseal woven bone without breakdown of the cartilage matrix following vascular invasion of chondrocyte lacunae. In situ hybridization revealed that the extending hypertrophic chondrocytes expressed type I and type II collagen mRNA, as well as that of type X collagen and that the osteoblasts in the metaphysis expressed type II and type X collagen mRNA, in addition to type I collagen mRNA. The topographic distribution of the signals suggests a possible co-expression of each collagen gene in the individual cells. Immunohistochemically, an overlapping deposition of type I, type II, and type X collagen was observed in both the extending cartilage and metaphyseal bony trabeculae. Such aberrant gene expression and synthesis of collagen indicate that pathologic ossification takes place in the epiphyseal/metaphyseal junction of oc/oc mouse femur in different way than in normal endochondral ossification. This abnormality is probably not due to a developmental disorder in the epiphyseal plate but to the failure in conversion of cartilage into bone, since the epiphyseal plate otherwise appeared normal, showing orderly stratified zones with a proper expression of cartilage-specific genes.

Animals↗
PubMed2006

Treatment of deep infection of total knee arthroplasty using a two-stage procedure.

OBJECTIVE: Treatment of deep infection of total knee arthroplasty by two-stage reimplantation. Using an articulating spacer may reduce the disadvantages of a static spacer (ligament contracture, muscle atrophy, muscle contraction, arthrofibrosis, and bone loss). Restoration of pain-free loading and ability to walk. INDICATIONS: Late deep infection after total knee arthroplasty. DEFINITION: infection occurring at least 6 weeks after the initial arthroplasty. CONTRAINDICATIONS: Large metaphyseal bony defects of the distal femur and proximal tibia. Missing or insufficient extensor mechanism. SURGICAL TECHNIQUE: The articulating spacer is made intraoperatively by cleaning and autoclaving the explanted femoral component and the tibial polyethylene insert. These components are reinserted by "press-fit cementing" without cement interdigitation into the trabecular bone. The cement is loaded with antibiotic during the same operation (2-4 g antibiotics per 40 g of cement powder). POSTOPERATIVE MANAGEMENT: With the articulating spacer in place, partial weight bearing with crutches and continuous passive motion daily up to a flexion of 90 degrees are allowed. Usually, reimplantation with a standard revision system is scheduled for 6-12 weeks after spacer implantation. RESULTS: In a prospective study 33 consecutive patients were treated from February 2000 to July 2003. The average period of hospitalization after spacer implantation was 14 days (8-26 days). Three patients had recurrent infection (success rate 91%) after a mean follow-up period of 28 months (12-48 months). The average Hospital for Special Surgery Knee Score could be increased from 67 points (44-84 points) preoperatively to 87 points (53-97 points) after reimplantation. The complications were one temporary peroneal palsy, one dislocation of the spacer due to the absence of the extensor ligaments, and one fracture of the tibia due to substantial primary metaphyseal bone loss.

Adult↗
PubMed2004

[Mechanical failure of porous hydroxyapatite ceramics 7.5 years after implantation in the proximal tibial].

The treatment of osseous defects is widely established in the elderly. The number of positive reports on the successful application of bovine as well as coralline hydroxyapatite ceramics has continuously increased during the last few years. In trauma surgery hydroxyapatite ceramics are most commonly applied in metaphyseal defects evoked by traumatic fractures of the long bones. The bovine and coralline materials applied are biocompatible and exhibit an interconnecting porous system. Good osteoconductive properties of such materials have repeatedly been demonstrated. Due to possible harmful effects caused by abrasion of the material, intra-articular application should be strictly avoided. Biological degradation of the materials does not occur even during long-term follow-up. The application of hydroxyapatite ceramics was introduced at our institution in 1992. Since then, no adverse events have been observed and only a few relevant complications were described in the literature. We report on a patient revealing a mechanical failure of a bovine hydroxyapatite (Endobon) 7.5 years after implantation into a metaphyseal defect of the proximal tibia caused by a traumatic fracture.

Athletic Injuries↗
PubMed2004

[Use of the injectable bone cement Norian SRS for tibial plateau fractures. Results of a prospective 30-month follow-up study].

Reduction of the depressed joint surface in tibial plateau fractures often leaves large cancellous bone defects. These metaphyseal voids are typically filled with autogenous bone grafts that can cause a significant donor site morbidity. The use of injectable bone cement offers the opportunity to support the reduced joint surface without bone grafting. The aim of this study was to evaluate the clinical and radiological outcome as well as the period of partial weight bearing after the use of Norian SRS in tibial plateau fractures. Twenty-one patients with a mean age of 48 years were included in this prospective trial. According to the AO/OTA Classification, there were seven fractures of type B2, ten B3, one C1, one C2, and two fractures of type C3. The period of partial weight bearing was 3.7 weeks. In 18 patients the follow-up was more than 24 months. After a mean follow-up of 30 months, the Lysholm score was 87.9 at mean. The radiological part of the Rasmussen score was excellent and good in eight cases each and fair in four cases. Soft tissue reactions due to the cement were not observed. On all radiographs taken 36 months after the operation the cement bloc was still visible. The results show that Norian SRS can be used to fill metaphyseal bone defects in tibial plateau fractures. Clinical and radiological results are comparable to those of fractures treated with autologous bone graft. The high compression strength allows early full weight bearing without the risk of secondary loss of reduction.

Adult↗
PubMed2005

[Cementless stems of the hip. Current status].

Optimal fixation of cementless stems is a precondition for long-lasting stability. Thus, anchorage, stabilizers, material and surface are of essential importance. To achieve primary stability, good rotational, tilting and axial stability is necessary. Stabilizers such as fins and ribs optimize stability. The CCD-angle and length of neck-axis determine the offset (laterality), leg-length and center of rotation. The stem, is responsible for the fixation of the prosthesis and for transmitting forces to the bone. The types of fixation are epiphyseal (the femoral head is covered by a cup prosthesis), metaphyseal and meta-diaphyseal (with straight or anatomically shaped monoblock-prostheses of different lengths, modular and custom-made prostheses) and diaphyseal (using predominantly modular systems). Titanium alloys are the predominate material for cementless stems. The surfaces are generally corundum-blasted or plasma sprayed. For metaphyseal and meta-diaphyseal stems, survival rates from 95 to 98% have been reached after 15 years. Diaphyseal-fixed stems have mid-term survival-rates of 92-99%.

Arthroplasty, Replacement, Hip↗
PubMed2001

[Long-term results with the cement-free Spotorno CLS shaft].

This retrospective study reviews 298 sequential cementless CLS Spotorno stems, which achieved their primary fixation and bony in- or ongrowth predominantly in the metaphyseal region. The minimum follow-up was 10 years and the average follow-up 11.7 years (range 10-14). The mean age at surgery was 55.2 years (range 32.2-68.9). Of the patients, 76.2% (227 stems) were followed up: 172 patients (57.7%) underwent clinical and radiological examination and 52 patients (55 stems, 18.5%) were interviewed by telephone. Of 298 stems, 13 (4.4%) had been replaced in the mean time, only 6 stems (2.0%) because of an aseptic loosening. The evaluation included both clinical (Merle d'Aubigne and Harris hip score) and radiographic parameters (plain X-rays). The mean Merle d'Aubigne score was 16.7 points, and the mean Harris hip score was 94.3 points. Radiolucent lines were detected in 33.7%; 5.8% showed enlargement within the last 3 years. Focal osteolyses were present in 30.8% of patients; 2.9% had progressed within the last 3 years. At follow-up, one patient presented with new clinical and radiological evidence of aseptic stem loosening. The current study showed an aseptic loosening of the CLS stem in 2.3%, a good osseointegration and good functional score results in more than 90%. The primary fixation and bony in- or ongrowth predominantly in the metaphyseal region seems to achieve good clinical results. Wear is the main reason for the osteolytic changes. Frequent clinical and radiological follow-up is important to detect bone reactions and loosening of the stem.

Adult↗
PubMed2005

Changes in bone mass and bone turnover following tibial shaft fracture.

INTRODUCTION: Bone loss occurs in the regional bone following tibial shaft fracture. An earlier cross-sectional study showed that measurements made at the metaphyseal region of the tibia using peripheral quantitative computed tomography (pQCT) and the ultradistal region of the tibia using dual-energy X-ray absorptiometry (DXA) were the most responsive at monitoring this bone loss. Biochemical markers of bone turnover enable us to assess the activity of bone formation and resorption during fracture healing. The aim of this longitudinal study was to determine the pattern and distribution of bone loss and bone turnover following a tibial shaft fracture treated with either plaster cast or intramedullary nail. METHODS: Eighteen subjects underwent bone mass measurements using DXA at the tibia and hip and quantitative ultrasound (QUS) at the tibia and calcaneus of both limbs at 2 weeks, 8 weeks, 12 weeks and 24 weeks following fracture, with hip and tibia DXA measurements also performed at 52 weeks. Nine of the patients treated with plaster cast had pQCT measurements at the tibia at 24 weeks. We measured three bone formation markers, bone alkaline phosphatase (bone ALP), osteocalcin (OC) and procollagen type 1 N-terminal peptide (PINP), a marker of bone resorption, serum C-telopeptides of type 1 collagen (beta-CTX) and a marker of collagen III turnover, procollagen type III N-terminal peptide (PIIINP) at 1 day, 3 days and 7 days and at 2, 4, 8, 12, 16 and 24 weeks following fracture. The greatest bone losses were observed at the ultradistal region of the tibia using DXA (28%, p <0.001) and the metaphyseal region of the tibia using pQCT (26-31%, p <0.001) at 24 weeks. In the hip, the greatest loss was in the trochanter region at 24 weeks (10%, p <0.001). The greatest loss at the calcaneus measured using QUS was for broadband ultrasound attenuation (BUA) measured using CUBA Clinical at 24 weeks (13%, p =0.01). RESULTS: At 1 year, there was a small recovery in bone loss (ultradistal tibia DXA, 20%, p <0.01; trochanter DXA 9%, p <0.001). Bone turnover increased following fracture (PINP +72+/-21%, p <0.0001, bone ALP +199+/-22%, p =0.004, beta-CTX +105+/-23%, p <0.0001, all at 24 weeks). There was a smaller +33+/-10% increase in osteocalcin at 24 weeks. PIIINP concentration peaked at week 8 (+57+/-9%, p <0.0001). The bone resorption marker beta-CTX showed an earlier rise (week 2, 139+/-33%) than the bone formation markers. CONCLUSIONS: We conclude that: (1) bone loss following tibial shaft fracture occurs both proximal and distal to the fracture; (2) the decreased BMD is largest for trabecular bone in the tibia with similar measurements using DXA and pQCT; (3) there is limited recovery of bone lost at the hip and tibia at 1 year; (4) tibial speed of sound (SOS) demonstrated a greater decrease than calcaneal SOS when comparing z -scores; (5) BUA is the QUS variable that shows the biggest decrease of bone mass at the calcaneus; (6) increase in bone turnover occurs following fracture with an earlier increase in bone resorption markers and a later rise in bone formation markers.

Absorptiometry, Photon↗
PubMed2006

Effects of spinal cord injury on osteoblastogenesis, osteoclastogenesis and gene expression profiling in osteoblasts in young rats.

INTRODUCTION: Spinal cord injury (SCI) causes a significant amount of bone loss in the sublesional area in animals and humans, and this type of bone loss is different from other forms of osteoporosis such as disuse osteoporosis and postmenopausal osteoporosis. However, no data is available on the cellular and molecular changes of osteoblastogenesis and osteoclastogenesis during SCI-induced bone loss. METHODS: SCI and SHAM rats were used in this study to investigate osteoblastogenesis and osteoclastogenesis in bone-marrow culture. We also measured bone mass and bone histomorphometry, as well as the expression of alkaline phosphatase (ALP), core binding factor alpha1 (Cbfa-1), osterix, receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in osteoblast-like cells in bone-marrow culture obtained from SCI and SHAM rats. RESULTS: Bone mineral density (BMD) measurement showed serious bone loss in the tibial ephiphyses and metaphyses of SCI rats compared with SHAM rats. In addition, bone histomorphometry analysis of the tibial metaphyses of SCI rats demonstrated that bone microarchitecture in SCI rats deteriorated further than in SHAM rats, and increased eroded surfaces and bone formation rates were observed in SCI rats. The number of osteoclasts that developed from bone marrow of SCI rats at equal density was significantly increased compared with SHAM rats, and the area of the resorption pits formed in the bone marrow culture from SCI rats was significantly greater than SHAM rats, whereas the number of CFU-F and CFU-OB was similar in both groups. RANKL mRNA and protein levels in osteoblast-like cells in culture obtained from SCI rats were significantly higher than those from the SHAM rats, whereas OPG levels decreased slightly. The ratios of RANKL to OPG expression in SCI rats were significantly higher than those in SHAM rats. However, osteogenic gene profiling of Cbfa-1, ALP and osterix in SCI rats remained similar with SHAM rats. CONCLUSION: These changes favor increased osteoclast activity over osteoblast activity, and may explain, in part, the imbalance in bone formation and resorption following SCI.

Alkaline Phosphatase↗
PubMed1999

Effects of menopause on age-dependent bone loss in the axial and appendicular skeletons in healthy Japanese women.

To determine the effects of menopause on bone loss in different parts of the skeleton, bone mineral density (BMD) values were measured longitudinally in 85 healthy women. BMD values included the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) and quantitative CT (QCT) and the distal and midradius measured by DXA obtained over 5 years. BMD at the calcaneus was measured using DXA for 3 years, and the BMD values of the distal metaphyses and diaphyses of radius and tibia were measured using peripheral QCT (pQCT) for 4 years. The subjects were 19 premenopausal, 17 perimenopausal, 12 early postmenopausal and 38 late postmenopausal women with the respective average ages of 39.1 +/- 7.1 (SD), 51.9 +/- 2.9, 55.8 +/- 1.8 and 61.9 +/- 3.9 years at the start of measurement. Average years since menopause were 1.4 +/- 1.8, 3.3 +/- 1.3 and 12.7 +/- 5.3 years, respectively. In the perimenopausal group, the annual rate of bone loss for lumbar trabecular bone measured by QCT, and for the calcaneus, and metaphyseal trabecular bone at the radius and tibia by pQCT were higher than the respective values in the premenopausal group. These values in the late postmenopausal group became significantly lower compared with those in the perimenopausal group, coming down to the level of the premenopausal group. While the annual rates of bone loss at the tibial diaphysis in the perimenopausal group were also higher than those in the premenopausal group, the values at the radial diaphysis by DXA or pQCT did not differ significantly. The reductions in the annual rates of bone loss with the passage of time after menopause were not marked in these cortical bone dominated sites. These data indicated that the annual rates of bone loss at trabecular bone dominated sites were accelerated in both axial and appendicular skeletons. Diaphyseal cortical bone, however, seemed to be less sensitive to estrogen withdrawal. Other factors, such as genetics and calcium/vitamin D metabolism, would also affect the age-dependent bone loss at the cortical bone dominated sites after menopause.

Absorptiometry, Photon↗
PubMed2005

Effect of ethane-1-hydroxy-1,1-bisphosphonate (EHBP) on endochondral ossification lesions induced by a lethal oral dose of uranyl nitrate.

A 350 mg/kg body weight (b.w.) oral dose of uranyl nitrate (UN) caused 100% mortality in mice three days after administration, due to resulting kidney lesions. Mortality decreased 50% after an oral (o) or subcutaneous (sc) dose of bisodic etidronate (EHBP). Given that bone is also a target organ for uranium (U) in acute intoxication, the aim of this work was to study the effect of exposure to a lethal oral dose of UN on endochondral ossification, and the latter's response to EHBP treatment. One hundred male Balb/c mice weighing 25 g were assigned to one of ten groups. Group I served as control. Group II received a lethal 350 mg/kg b.w. oral dose of UN by gavage. Groups III, IV, VII, and VIII received an equal dose of UN immediately followed by a single 500 mg/kg oral dose of EHBP in groups III and VII and a single 50 mg/kg subcutaneous dose of EHBP in groups IV and VIII. Groups V and IX only received a single 500 mg/kg oral dose of EHBP, and groups VI and X received a single 50 mg/kg subcutaneous dose of EHBP. The animals in groups II, III, IV, V, and VI were sacrificed 48 h after the onset of the experiment, whereas those in groups VII, VIII, IX, and X were killed at 14 days. Histologic and histomorphometric studies were performed on the femurs to determine growth cartilage width, bone volume, and metaphyseal bone activity. Our results showed that all growth cartilage and metaphyseal bone histomorphometric parameters were significantly lower in animals exposed to UN at 48 h than in controls. EHPB administration was found to prevent this condition at 48 h reaching similar values to those of controls. Although histomorphometric values did not reach control values at 14 days, they were higher than those of animals exposed to UN at 48 h not treated with EHBP. It is noteworthy that these values also decreased in animals only receiving EHBP at 14 days. Our results show that EHBP effectively ameliorates the adverse effects of a lethal dose of UN on endochondral ossification.

Administration, Oral↗
PubMed2002

Effect of alendronate on periprosthetic bone loss after total knee arthroplasty: a one-year, randomized, controlled trial of 19 patients.

Undesired bone loss around implants is considered to occur mainly because of a stress-shielding phenomenon. Bone surrounding the total knee arthroplasty (TKA) adjusts its mineral density and structure to meet new mechanical demands. Immobilization, in combination with local operative trauma to the bone and soft tissues, has an additional impact on bone loss. The clinical survival of TKA is associated with the quality and quantity of the surrounding bone environment. Poor bone quality and quantity may predispose to aseptic implant loosening and periprosthetic fractures. We investigated the efficacy of oral bisphosphonate (alendronate, Fosamax) with calcium (Calcichew) for the inhibition of early bone mineral density (BMD) loss after TKA in a prospective, randomized, one-year follow-up study. Periprosthetic BMD changes were measured with fan-beam dual-energy X-ray absorptiometry (DXA) in 19 patients with knee osteoarthrosis. Patients (n = 8) treated with 10 mg alendronate and 500 mg calcium daily maintained distal femoral BMD values close to the baseline values (P > 0.04), while patients receiving only 500 mg of calcium daily (n = 11) showed significant bone loss during the one-year follow-up (P < 0.015). The treatment groups differed significantly in metaphyseal anterior, posterior, diaphyseal, and metaphyseal total regions of interest (ROIs) (repeated measures ANOVA analyses, P = 0.019, P = 0.010, P = 0.022, and P = 0.024, respectively). Our results indicate that oral alendronate reduces early postoperative periprosthetic bone loss significantly. This therapeutic strategy may improve the results and longevity of primary total knee arthroplasties.

Absorptiometry, Photon↗
PubMed2003

Fourier transform infrared imaging spectroscopy (FT-IRIS) of mineralization in bisphosphonate-treated oim/oim mice.

Fourier transform infrared microscopy (FT-IRM) and imaging spectroscopy (FT-IRIS) are increasingly used to analyze the molecular components of mineralized tissues. A primary advantage of these techniques is the capability to simultaneously image the quantity and quality of multiple components in histological sections at 7 microm spatial resolution. In the current study, FT-IRM and FT-IRIS were used to characterize bone mineralization in a mouse model of osteogenesis imperfecta (OI) after treatment with the bisphosphonate alendronate (ALN). This application is currently relevant since recent studies have demonstrated great promise for the treatment of children with OI with bisphosphonates, but have not identified bisphosphonate-associated bone quality changes. Growing oim/oim mice, a model of moderate-to-severe OI, were treated with ALN (73 microg ALN/kg/day for 4 weeks followed by 26 mg/kg/day for 4 weeks) or saline from 6 to 14 weeks of age, and mineralization was evaluated in femoral cortical and metaphyseal bone. Infrared vibrations of the mineral (a carbonated apatite) and the matrix phases were monitored. The relative amounts of mineral and matrix present (min:matrix), the relative amount of carbonate present in the mineral (carb:min), and the crystallinity of the mineral phase were calculated. In untreated oim/oim bone, the min:matrix was greater and the crystallinity was reduced (indicative of less mature mineral) in the primary versus the secondary spongiosa, most likely due to the presence of calcified cartilage. With ALN treatment, the oim/oim mm:matrix increased in the secondary spongiosa, but the mineral crystallinity was not changed. In the cortical bone, no changes were evident with ALN treatment. These data demonstrate that in this mouse model, ALN treatment results in increased metaphyseal bone mineralization, but does not improve mineral maturity.

Alendronate↗
PubMed2002

Ultrastructural distribution of osteoadherin in rat bone shows a pattern similar to that of bone sialoprotein.

Osteoadherin (OSAD) is a keratan sulfate proteoglycan recently isolated from bovine and rat bone. Based on results obtained from in vitro experiments, the protein was shown to bind osteoblasts via the integrin receptor alpha v beta 3. Due to OSAD's capacity to bind hydroxyapatite crystals, a role for the protein in the mineralization process has also been suggested. To test these hypotheses in an in vivo model, the ultrastructural localization of OSAD in bone, tibial (metaphyses and diaphyses), and calvarial samples from normal 10 to 12-day-old rats were examined by immunohistochemical techniques at the ultrastructural level. In addition to the qualitative studies, quantitative measurements of OSAD marker density were performed in relevant compartments. Immunolabeling for OSAD was located to the mineralized bone matrix, with highest concentration of marker at the border between bone and cartilage remnants in the metaphyseal trabeculi. Intracellular labeling was low and no systemic accumulation of OSAD markers was observed at the cell-matrix interface. The observed distribution pattern of OSAD is strikingly similar to that of bone sialoprotein (BSP), confirmed by double labeling. The results of the current study support a role for OSAD in the mineralization process. In this process BSP is assumed to be a nucleator of hydroxyapatite crystals, and OSAD could work in concert with BSP to regulate nucleation. However, the mechanisms involved remain to be elucidated.

Animals↗
PubMed2006

PIXImus bone densitometer and associated technical measurement issues of skeletal growth in the young rat.

The PIXImus dual-energy X-ray absorptiometer (DXA) is designed to measure body composition, bone mineral content (BMC), area (BA), and density (BMD) in mice and rats. The aims of this study were to longitudinally measure BMC, BA, and BMD in growing rats and to identify potential technical problems associated with the PIXImus. Total femur and lumbar DXA measurements, body weight, and length of initially 3-week-old rats (n = 10) were taken at weeks 5, 9, and 14. BMC and BMD of femoral metaphyseal and diaphyseal regions rich in trabecular and cortical bone, respectively, were obtained. Results showed significant increases in body weight, total femur BMC and BMD, lumbar area, length, BMC, and BMD at each time point. There was a significant positive correlation between body weight and total femur BMD (r = 0.97, P < 0.001) as well as lumbar BMD (r = 0.99, P < 0.001). BMD values for the femoral metaphyseal region and the lumbar spine were also positively correlated (r = 0.96, P < 0.01). Several technical issues (e.g., positioning of animals), difficulties (e.g., in analysis of images), and limitations (e.g., inability to detect underdeveloped calcified bone in growing animals and bone edge detection) of the software pertinent to the PIXImus were evident. In conclusion, despite limitations in the software, the PIXImus is a valuable tool for studying skeletal development of growing rats.

Absorptiometry, Photon↗