Osteoid Seam Width Research Articles

Osteomalacia Prevalence, Biochemical Profile, and Histology in Patients with Low-Energy Hip Fractures Over the Age of 45.

Our objective was to determine the prevalence of osteomalacia in low-energy hip fracture patients over the age of 45, based on biochemical and histological measures. This cross-sectional study included 72 patients over 45 with low-energy mechanism hip fractures. Samples of fasting venous blood were taken for hemograms and serum biochemistry analyses. Bicortical biopsies of the iliac crest were obtained, processed, and evaluated by an expert pathologist for osteomalacia. Biochemical osteomalacia (b-OM) is defined according to a distinct criterion. A low level of serum calcium, phosphorus, albumin, and 25OHD was found in 43.1, 16.7, 73.6, and 59.7% of patients, respectively. 50.0% of patients had high serum alkaline phosphatase (ALP) levels. b-OM was found in 30 (41.7%), and no significant association was found with PTH, Cr, Alb, age, sex, fracture type, side of the trauma, and season were not associated with osteomalacia. Osteomalacia was diagnosed on histopathological analysis in 19/72 (26.7%), and 54/72 (75.0%) of all cases fulfilled b-OM criteria. In the histologic evaluation, osteoid seam width, osteoid surface, and osteoid volume were 28.5µm, 25.6, and 12.1%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the biochemical test for detecting osteomalacia were 73.6, 64.2, 42.4, 87.2, and 66.7%, respectively. Up to 30% of elderly patients with low-energy hip fractures are affected by osteomalacia. A biochemical screening along with a bone biopsy and histopathologic evaluation may be logical in a high-risk population for osteomalacia diagnosis.

Unveiling the Metabolic Mystery of Fragility Hip Fracture in Indian Patients: A Histomorphometric and Biochemical Correlation.

High prevalence of hypovitaminosis D is being reported in Indian patients with fragility hip fracture. The gold standard to diagnose osteoporosis and osteomalacia is bone histomorphometry. There is no study evaluating histopathological histomorphometry in Indian fragility hip fracture patients. The purpose of the study was to evaluate fragility hip fracture patients for histopathological osteomalacia and osteoporosis by histomorphometry and to correlate histopathological findings with biochemical hypovitaminosis D. A total of 55 patients of fragility hip fractures recruited for prospective cross-sectional study. During definitive fracture fixation of these fragility hip fractures, bone biopsy taken from neck region of femur by a novel approach for histomorphometry. Histomorphometric analysis was based on three indices, namely osteoid seam width, osteoblast surface, and osteoid surface. We also analysed blood bone biochemistry and correlated with bone histomorphometry. In fragility hip fracture patients, the prevalence of histomorphometric osteoporosis and osteomalacia were very low (only 9.4% had osteoporosis and none had osteomalacia) however in blood bone biochemistry, we found high prevalence (85.5%) of hypovitaminosis D. We also noted significant changes when correlated bone histomorphometry with different blood bone biochemistry. Indian patients with fragility hip fracture were found to have high prevalence of biochemical hypovitaminosis D but unlike western literature, there was low prevalence of histomorphometric osteoporosis with no evidence of histomorphometric osteomalacia. Correct knowledge about metabolic status of fragility hip fracture is required to improve outcome, decrease complications and to optimise cost of the treatment.

Evaluation of a bioengineered ACL matrix's osteointegration with BMP-2 supplementation.

A poly (l-lactic) acid bioengineered anterior cruciate ligament (ACL) matrix has previously demonstrated the ability to support tissue regeneration in a rabbit ACL reconstruction model. The matrix was designed for optimal bone and ligament regeneration by developing a matrix with differential pore sizes in its bone and ligament compartments. Building upon past success, we designed a new bioengineered ACL matrix that is easier to install and can be used with endobutton fixation during ACL reconstruction. To achieve this, a new braiding procedure was developed to allow the matrix to be folded in half, making two-limbs, while maintaining its bone and ligament compartments. The osteointegration of the matrix with and without bone morphogenetic protein 2 (BMP-2) supplementation was evaluated in a rabbit ACL reconstruction model. Two doses of BMP-2 were evaluated, 1 and 10 μg, and delivered by saline injection into the bone tunnel at the end of surgery. A fibrous matrix-to-bone interface with occasional Sharpey’s fibers was the primary mode of osteointegration observed. The matrix was also found to support a fibrocartilage matrix-to-bone interface. In some cases, the presence of chondrocyte-like cells was observed at the aperture of the bone tunnel and the center of the matrix within the bone tunnel. Treatment with BMP-2 was associated with a trend towards smaller bone tunnel cross-sectional areas, and 1 μg of BMP-2 was found to significantly enhance osteoid seam width in comparison with no BMP-2 or 10 μg of BMP-2 treatment. Regenerated tissue was well organized within the bioengineered ACL matrix and aligned with the poly (l-lactic) acid fibers. Disorganized tissue was found between the two-limbs of the bioengineered ACL matrix and hypothesized to be due to a lack of structural scaffolding. This study suggests that the bioengineered ACL matrix can undergo similar modes of osteointegration as current autografts and allografts, and that BMP-2 treatment may enhance osteoblastic activity within the bone tunnels.

Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis.

This study aims to explore the effects of exercise on postmenopausal osteoporosis and the mechanisms by which exercise affects bone remodeling. Sixty-three Wistar female rats were randomly divided into five groups: (1) control group, (2) sham-operated group, (3) OVX (Ovariectomy) group, (4) DES-OVX (Diethylstilbestrol-OVX) group, and (5) Ex-OVX (Exercise-OVX) group. The rat osteoporosis model was established through ovariectomy. The Ex-OVX rats were made to run 251.2 meters every day, 6 d/wk for 3 months in a running wheel. Trabecular bone volume (TBV%), total resorption surface (TRS%), trabecular formation surface (TFS%), mineralization rate (MAR), bone cortex mineralization rate (mAR), and osteoid seam width (OSW) were determined by bone histomorphometry. The mRNA and protein levels of interleukin-1β (IL-1β2), interleukin-6 (IL-6), and cyclooxygenase-2 (Cox-2) were determined by in situ hybridization and immunohistochemistry, respectively. Serum levels of estrogen estradiol (E2), calcitonin (CT), osteocalcin (BGP), and parathyroid hormone (PTH) were determined by ELISA assays. The investigation revealed that compared to the control and the sham-operated groups, the OVX group showed significantly lower levels of TBV%, E2, and CT, but much higher levels of TRS%, TFS%, MAR, OSW, BGP, and PTH. The Ex-OVX group showed increased TBV% and serum levels of E2 and CT compared to the OVX group. Ovariectomy also led to a significant increase in IL-1β mRNA and protein levels in the bone marrow and IL-6 and Cox-2 protein levels in tibias. In addition, the Ex-OVX group showed lower levels of IL-1 mRNA and protein, IL-6 mRNA, and Cox-2 mRNA and protein than those in the OVX group. The upshot of the study suggests that exercise can significantly increase bone mass in postmenopausal osteoporosis rat models by inhibiting bone resorption and increasing bone formation, especially in trabecular bones.

Validity of the DEXA diagnosis of involutional osteoporosis in patients with femoral neck fractures

Background:There exists no study comparing dual energy X-ray absorptimetry (DEXA) with histomorphometry to evaluate its accuracy and validity as an assessment tool. A prospective study was done comparing the measurements of osteoporosis in patients with femoral neck fractures using the histological method of diagnosis and in the same patients with DEXA postoperatively.Patients and Methods:The histological method depends on histomorphometric analysis of bone biopsies taken from the neck of femur during surgical treatment of the fracture. We depend on three indices in histomorphometric analysis: these are osteoid seam width, osteoblast surface, and osteoid surface. The radiological method depends on the measurement of the bone mineral density using DEXA for fractured patients with the scan performed onto the contralateral nonfractured hips and lumbar spines.Results:We found positive histological histomorphometric parameters of osteoporosis in 68% of patients with the femoral neck fracture, and there is a moderate correlation between histological histomorphometric analysis and DEXA in the diagnosis of osteoporosis in these patients. In our study, DEXA can detect up to 88.2% of possible cases of osteoporosis (sensitivity 88.2%), but the specificity of this diagnostic tool is 62.5% at a t-score of ≤ −2, i.e., it is sensitive but less specific. The mean difference in the t-score in femoral DEXA and lumbar DEXA is almost zero.Conclusions:DEXA is a noninvasive and an affordable and easy method for the diagnosis of osteoporosis but less efficient than the histological histomorphometric method of diagnosis with a low specificity. We also found that the mean difference in the t-score in femoral DEXA and lumbar DEXA is almost zero, so DEXA of one region can reflect the change in the other region and there is no need for DEXA of both regions as a routine unless indicated for a special reason. This avoids exposing the patient to unnecessary risk of radiation and reduces cost.

Tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys ( Macaca mulatta)

The acyclic nucleoside phosphonate analog, 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA; Tenofovir; Gilead Sciences, Inc., Foster City, CA), has been shown to effectively inhibit simian immunodeficiency virus (SIV) replication in rhesus macaques by blocking reverse transcription. However, chronic long-term tenofovir treatment at 30 mg/kg/day, intended to reduce viral replication and illness, has been shown to result in bone deformities and spontaneous fractures in rhesus monkeys. Based on these findings, we studied the effects of tenofovir treatment and pathogenic SIV infection on cortical bone remodeling in rhesus monkeys. Tibiae from tenofovir-treated or untreated, SIV-infected or uninfected, rhesus macaques were evaluated for bone microdamage and remodeling. We found that tenofovir treatment had a significant effect on osteoid (unmineralized bone) seam width in tibial cross-sections. Regardless of SIV infection status, half of the tenofovir-treated animals had significantly increased osteoid seam widths in tibial cortical bone resulting in an osteomalacia-like condition. Pathogenic SIV infection significantly increased tibial resorption cavity density, and this increase was normalized by tenofovir treatment. These results suggest that tenofovir treatment at 30 mg/kg/day inhibits mineralization of newly formed bone. SIV infection results in increased tibial resorption cavity density, while tenofovir treatment tends to minimize this increase. Both defective mineralization of newly formed bone and increased resorption cavity density may result in greater bone fragility.

Subchondral bone thickness, hardness and remodelling are influenced by short-term exercise in a site-specific manner

It was hypothesised that subchondral bone thickness, hardness and remodelling are influenced by exercise intensity, and by location within a joint. Dorsal carpal osteochondral injury is a major cause of lameness in horses undergoing high intensity training. This project aimed to determine the subchondral bone thickness, formation, resorption and hardness at sites with high and low incidence of pathology in 2 year-old horses undergoing 19 weeks high intensity treadmill training or low intensity exercise, and to compare these factors between exercise groups. Dorsal and palmar test sites were identified on radial, intermediate and third carpal articular surfaces after euthanasia. Adjacent osteochondral samples from each test site underwent histomorphometric analysis (for subchondral bone thickness, osteoid perimeter, osteoid seam width, eroded cavity area and eroded cement line surface length) and microhardness testing. Bone from horses undergoing high intensity training was thicker with a greater osteoid perimeter, and at individual sites had a smaller osteoid seam width and eroded cavity. Exercise-related differences were most marked at dorsal locations. Maximal differences in bone formation indices were observed at dorsal radial and medial third carpal locations. Overall subchondral bone from dorsal sites was thicker with a greater osteoid perimeter. Subchondral bone from dorsal sites was approximately 35% harder than bone from palmar sites. These results show topographical variations in subchondral bone structure, formation, resorption and material properties and a site-specific response to exercise. The maximal response to exercise was at high load sites with a clinical predisposition to injury. These findings indicate that the combined effect of exercise and local load variations within a joint may lead to maximal adaptive responses or overload of these responses at sites predisposed to injury.

A histomorphological investigation of the effect of cyclosporin on trabecular bone of the rat mandibular condyle

The effect of cyclosporin A (CSA) on the condylar trabecular bone was evaluated by microscopy. Twenty, 5-week-old male Sprague–Dawley rats were divided into a treated and a control group. Animals in the treated group received CSA, 15 mg/kg body weight, by gastric feeding daily for 4 weeks; controls received the vehicle only. Five animals from each group were killed at the end of weeks 2 and 4. After histological processing, 10 tissue sections from the mid-part of the mandibular condyle were examined. Generally, a histopathological osteopenia was observed around the condyle after CSA treatment, especially at the end of week 4. In the control animals, the trabecular bone volume steadily increased from weeks 2 to 4 (from 0.46±0.07 to 0.61±0.07 mm 3/mm 3). However, the bone volume was significantly less in the CSA group than in the control group at both times (0.33±0.02 vs 0.46±0.07 and 0.26±0.07 vs 0.61±0.07 mm 3/mm 3 for CSA vs control group at the end of weeks 2 and 4, respectively). Conversely, an increased marrow volume was observed in the CSA group at both these times (0.60±0.02 vs 0.42±0.08 and 0.71±0.06 vs 0.31±0.06 mm 3/mm 3 for CSA vs control group at the end of weeks 2 and 4, respectively). Decreases were also observed in trabecular thickness, osteoid seam width, osteoid volume and cortical bone width. Because trabecular bone mass, osteoid mass and cortical bone thickness all showed a decrease after CSA at both times, an inhibitory effect of CSA on trabecular bone formation in the mandibular condyle is proposed.

Mechanism of Bone Loss After Liver Transplantation: A Histomorphometric Analysis

Organ transplantation is associated with increased bone loss and high fracture risk, but the pathophysiological mechanisms responsible have not been established. We have performed a histomorphometric analysis of bone remodeling before and 3 months after liver transplantation in 21 patients (14 male, 7 female) aged 38-68 years with chronic liver disease. Eight-micrometer undecalcified sections of trans-iliac biopsies were assessed using image analysis. Preoperatively, bone turnover was low with a tendency toward reduced wall width and erosion depth. The bone formation rate increased from 0.021 +/- 0.016 (mean +/- SD) to 0.067 +/- 0.055 microm2/microm/day after transplantation (p < 0.0002) and activation frequency from 0.24 +/- 0.21/year-1 to 0.81 +/- 0. 67/year-1 (p < 0.0001). No significant change was observed in wall width, but there was a trend toward an increase in indices of resorption cavity size. There was a small increase in osteoid seam width postoperatively (p< 0.02) and decrease in mineralization lag time (p < 0.001). No significant changes in indices of cancellous bone structure were observed in the postoperative biopsies. These results demonstrate a highly significant and quantitatively large increase in bone turnover in the first 3 months after liver transplantation. Although no significant disruption of cancellous bone structure was demonstrated during the time course of the study, the observed changes in bone remodeling predispose to trabecular penetration and may thus result in long-term adverse effects on bone strength.

The effects of long-term hormone replacement therapy on bone remodeling in postmenopausal women

Hormone replacement therapy prevents menopausal bone loss and reduces the risk of fragility fracture, but its effects on bone remodeling have not been clearly established. We studied the effects of long-term hormone replacement therapy on bone turnover and remodeling balance in 22 post-menopausal women with osteopenia or osteoporosis. Iliac crest biopsies were obtained before and after treatment (mean 23.5 months) after double tetracycline labeling and subjected to histomorphometric analysis. Post-treatment biopsies showed a significant reduction in bone formation rate at tissue level and activation frequency ( p = 0.002 and 0.01, respectively). There was also a reduction in mineral appositional rate ( p = 0.0002) and osteoid seam width ( p = 0.01), but no significant change in mineralization lag time or osteoid maturation period. Wall width showed a significant decrease after treatment ( p = 0.03) and there was a consistent trend toward a reduction in resorption cavity dimensions with a statistically significant decrease in the resorption cavity length ( p = 0.03). These results confirm the previously reported reduction in bone turnover in postmenopausal women treated with hormone replacement therapy. Post-treatment biopsies also showed a reduction in resorption cavity size and a decrease in wall width, the latter possibly reflecting a compensatory change in response to the reduction in erosion depth. Our data do not provide any evidence that conventional hormone replacement therapy has anabolic effects at the level of the bone remodeling unit and indicate that its beneficial skeletal effects result from suppression of bone turnover and a reduction in the size of resorption cavities.

Reduced bone formation in patients with osteoporosis associated with inflammatory bowel disease.

The pathophysiology of bone loss associated with inflammatory bowel disease has not been clearly defined. In this study we have performed a detailed histomorphometric analysis of iliac crest bone obtained from 19 patients with inflammatory bowel disease in whom a diagnosis of osteoporosis had been made. Eleven subjects were receiving prednisolone at the time of their biopsy. Comparison with control values demonstrated a highly significant reduction in trabecular bone area in the patient group (p < 0.001). Wall width, adjusted appositional rate and bone formation rate were all significantly reduced in the patient group (p < 0.001) and the formation period was significantly increased (p < 0.001). Resorption cavities were slightly smaller in the patient group, differences in maximum cavity depth and cavity length achieving statistical significance (p < 0.005 and p < 0.05 respectively). The mineral appositional rate was significantly reduced in the patients with inflammatory bowel disease (p < 0.001) and the mineralization lag time significantly increased (p < 0.001); however, osteoid area, perimeter and seam width were not significantly different from controls. These results demonstrate that osteoporosis associated with inflammatory bowel disease is characterized by reduced bone formation at the cellular and tissue level; the proportionately greater change in wall width than in resorption cavity depth is consistent with a negative remodelling balance. Although none of the patients had osteomalacia as defined by the criteria of increased osteoid seam width and mineralization lag time, the higher mineralization lag time in the patient group indicates a mild mineralization defect.

Distinction between focally accelerated bone formation and osteomalacia in carcinoma of prostate metastasised to bone.

We studied the histological indices of skeletal turnover in 40 patients with carcinoma of the prostate and skeletal metastases in order to determine the prevalence of osteomalacia. In 20 patients biopsied through uninvolved bone, the histological indices of bone turnover were normal. In particular, osteoid seam width and bone formation rates were consistently normal, indicating the absence of osteomalacia. In biopsies from tumour-laden bone, hyperosteoidosis was present, usually associated with increased amounts of woven collagen and consistently associated with high rates of bone formation and mineralisation. It was concluded that hyperosteoidosis in prostatic cancer is rarely due to osteomalacia.

Fixed membranous bone graft survival after recipient bed alteration.

The effectiveness of membranous bone grafting in craniofacial reconstruction is hindered by resorption. The aim of this study was to determine whether alterations of the recipient bed through tissue expansion affect membranous bone graft survival. Eighteen adult rabbits were divided into three groups. Group I rabbits (control) received fixed autologous membranous bone grafts to their snouts. Group II rabbits had self-inflating tissue expanders inserted over their nasal dorsum, inflation for 3 weeks, and then expander removal and placement of fixed autologous membranous bone grafts to their snouts. Group III rabbits varied from group II by delaying bone grafting until 2 weeks after expander removal. One animal from each group was killed at post-grafting days 15 and 45, the remainder at day 90. Results were assessed by volumetric, nondecalcified histologic, and stereologic analysis. Volumetrically, group I grafts demonstrated 82 percent survival, whereas group II demonstrated 101 percent (p = 0.029) and group III 94.5 percent (p = 0.21). Histologically, group I grafts exhibited greater loss (i.e., porosity and resorption) and less labeling activity. Groups II and III showed extensive evidence of trabecularization and incorporation at the graft-host interface. Stereologic measurements such as osteoid seam width (OSW) confirmed the greater survival and activity of groups II and III bone grafts. Group II OSW measured 12.4 microns, group III 12.0 microns, and group I 9.8 microns (p = 0.04). Stereology also demonstrated that groups II and III's OSW approached that of the recipient bed and contralateral zygoma, whereas group I did not (p = 0.029), suggesting an integration of the graft and host architectures.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of vitamin or mineral deficiency on the morphology of medullary bone in laying hens

Adult laying hens were fed diets deficient in phosphorus, calcium, calcium and phosphorus, and vitamin D 3 to determine their effects on bone histology and parathyroid gland size. The phosphorus deficient diet caused an insignificant decrease in parathyroid size while the other diets caused significant increases. A considerable amount of individual variation in medullary bone volume and osteoid seam width was observed in all groups but, despite this, the calcium, calcium and phosphorus and vitamin D 3 deficient diets clearly resulted in increased osteoid. Birds receiving diets deficient in calcium and phosphorus, and in vitamin D 3 for longer periods were observed to have partially or completely resorbed medullary bone. Osteodystrophia fibrosa was noted in vitamin D 3 deficient birds which had no follicular activity.

Low Prevalence of Osteomalacia in Elderly Patients with Hip Fracture

In order to establish the prevalence of osteomalacia in elderly patients with hip fracture, trans-iliac biopsies were obtained from 49 patients, aged 67-92 years, admitted to Cardiff Royal Infirmary with hip fracture. Undecalcified sections were quantitatively assessed and the diagnosis of osteomalacia was made when there was an increase in mean osteoid seam width (greater than 15 microns) associated with a reduction in calcification fronts (less than 60% of osteoid-covered surfaces). Osteomalacia was present in only one patient; in the remaining patients, osteoid surface extent, volume and mean seam width were within normal limits. Thus osteomalacia, when defined by rigorous histomorphometric criteria, was rare in these elderly subjects with hip fracture.

A model of osteon closure in cortical bone

A model of osteon closure is presented that incorporates some physiologic features of cortical bone remodeling, such as matrix synthesizing activity of osteoblasts, their burial as osteocytes, and elimination of cells. A simplified version of the model assumes a constant osteoblast activity throughout radial closure. An extended version allows for variable osteoblasts activity and is based on Lee's law of radial closure kinetics. The model calculations (extended model) show that both in humans and beagle dogs osteoblast activity steadily decreases during radial closure of the osteon. The potential of the model is also illustrated by calculating the dynamic change of the geometrical shape of the closing cone and the time dependence of the osteoid seam width, number of osteoblasts and bone formation rate in the closing cone.

Equivalency of various methods for estimating osteoid seam width.

We compared the true osteoid seam width (TOSW) as measured by a modification of the orthogonal intercept lengths with various methods of estimating seam widths, including (1) the commonly used length measurements at four equidistant points (O.Wi/4PT), (2) osteoid area divided by the osteoid perimeter (O.Ar/O/Pm) or the bone/osteoid interface (O.Ar/B.Bd), and (3) a novel method for estimating seam width defined as the osteoid area divided by the major axis of the seam (O.Ar/Axis). All methods for approximating osteoid seam width significantly exaggerated the true osteoid seam dimension by an amount that ranged from 16 to 23%. However, the relative accuracy of all methods of estimating osteoid seam width are equivalent as evidenced by the similar mean difference from the TOSW (3.4, 4.1, 5.1, and 3.8) demonstrated by O.Wi/5PT, O.Ar/Axis, O.Ar/O.Pm, O.Ar/B.Bd, respectively. Regression analysis of the various estimates of seam width on TOSW also demonstrated the equivalency of these methods. Moreover, all estimates could be employed to discriminate seams of normal dimensions from abnormally wide seams in bone specimens derived from patients with osteomalacia. Differences between the methods, however, were observed that may have practical importance. In this regard, the direct procedure of determining distance demonstrated less variance than the indirect estimate of width. As a result, the direct measurement required fewer samples (n = 13) to detect a significant difference to normal and could discriminate smaller deviations in seam width (1.7 microns) at a given sample size compared with O.Ar/Axis (n = 28; 2.9 microns), O.Ar/O.Pm (n = 42; 3.4 microns), and O.Ar/B.Bd (n = 42; n = 3.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Inflammation-mediated osteopenia (IMO) during acute inflammation in rats is due to a transient inhibition of bone formation.

Local inflammation was induced in rats through the subcutaneous injection of magnesium silicate. Trabecular bone volume of the tibia decreased progressively during a 3 week observation period following the inflammatory stimulus. The trabecular bone surface covered with osteoblasts was strikingly reduced during the first week but had normalized by the end of the third week. Calcification rate in the cortical bone of the tibia was reduced with a parallel reduction in endosteal osteoid seam width. Both calcification rate and tetracycline double-labeled surface of vertebral trabecular bone were reduced during the first 2 weeks. Neither total bone resorption surface nor active bone resorption surface were increased. There was a decrease in osteoclast numbers/mm2 bone tissue associated with decreasing bone volume. Our data demonstrate a transient inhibition of bone formation during acute inflammation in the rat and indicate that changes in osteoblast function are part of the acute phase response following local inflammation.

Thyroparathyroidectomy modifies the skeletal response to aluminum loading in the rat

Diminished parathyroid hormone (PTH) secretion may contribute to the accumulation of aluminum (Al) in bone and to impaired bone formation in Al-related bone disease. Therefore, intact (AL, N = 9) and thyroparathyroidectomized (TPTX-AL, N = 9) rats were given intraperitoneal injections of Al, 2 mg/day, for 42 days; intact control (C, N = 11) and TPTX control (TPTX-C, N = 9) animals received i.p. injections of vehicle only. Quantitative bone histology and measurements of mineralized bone formation (Rbf) using double tetracycline labeling were done for cortical and for trabecular bone; trabecular bone aluminum content (BA) was determined by histochemical methods. BA did not differ between AL and TPTX-AL, 33 +/- 13% versus 39 +/- 14%, and Rbf decreased similarly from control values in both Al-treated groups. In contrast, osteoid production was impaired to a greater extent in TPTX-AL than in AL. Thus, osteoid area and osteoid seam width were each lower in TPTX-AL than in TPTX-C; these values did not differ between AL and C. TPTX can aggravate Al induced reductions in osteoid synthesis, and low serum PTH levels may contribute to the pathogenesis of aplastic bone. However, reductions in Rbf during Al loading are not mediated by PTH.

Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in the pig.

Bone formation is impaired in aluminum-associated bone disease. Reductions in the number of osteoblasts or in the function of individual osteoblasts could account for this finding. Thus, quantitative bone histology and measurements of bone formation were done at three skeletal sites in piglets given aluminum (Al) parenterally, 1.5 mg/kg per d, for 8 wk (Al, n = 4) and in control animals (C, n = 4). Bone Al was 241 +/- 40 mg/kg per dry weight in Al and 1.6 +/- 0.9 in C, P less than 0.001. All Al-treated animals developed osteomalacia with increases in osteoid seam width, osteoid volume, and mineralization lag time at each skeletal site, P less than 0.05 vs. C for all values. Mineralized bone formation at the tissue level was lower in Al than in C, P less than 0.05 for each skeletal site, due to reductions in active bone forming surface. Bone formation at the cellular level was similar in each group, however, and total osteoid production by osteoblasts did not differ in C and Al. Aluminum impairs the formation of mineralized bone in vivo by decreasing the number of active osteoblasts, and this change can be distinguished from the effect of aluminum to inhibit, either directly or indirectly, the calcification of osteoid.