Deficient bone formation in idiopathic juvenile osteoporosis: a histomorphometric study of cancellous iliac bone.

Idiopathic juvenile osteoporosis (IJO), a rare cause of osteoporosis in children, is characterized by the occurrence of vertebral and metaphyseal fractures. Little is known about the histopathogenesis of IJO. We analyzed by quantitative histomorphometry iliac crest biopsies from 9 IJO patients (age, 10.0-12.3 years; 7 girls) after tetracycline labeling. Results were compared with identically processed samples from 12 age-matched children without metabolic bone disease and 11 patients with osteogenesis imperfecta type I. Compared with healthy controls, cancellous bone volume (BV) was markedly decreased in IJO patients (mean [SD]: 10.0% [3.1%] vs. 24.4% [3.8%]), because of a 34% reduction in trabecular thickness (Tb.Th) and a 37% lower trabecular number (Tb.N; p < 0.0001 each; unpaired t-test). Bone formation rate (BFR) per bone surface was decreased to 38% of the level in controls (p = 0.0006). This was partly caused by decreased recruitment of remodeling units, as shown by a trend toward lower activation frequency (54% of the control value; p = 0.08). Importantly, osteoblast team performance also was impaired, as evidenced by a decreased wall thickness (W.Th; 70% of the control value; p < 0.0001). Reconstruction of the formative sites revealed that osteoblast team performance was abnormally low even before mineralization started at a given site. No evidence was found for increased bone resorption. Compared with children with osteogenesis imperfecta (OI), IJO patients had a similarly decreased cancellous BV but a much lower bone turnover. These results suggest a pathogenetic model for IJO, in which impaired osteoblast team performance decreases the ability of cancellous bone to adapt to the increasing mechanical needs during growth. This will finally result in load failure at sites where cancellous bone is essential for stability.     

Computerized three-dimensional histomorphometric study of iliac bone in patients with femoral neck fracture

To elucidate the pathology of osteoporosis, we used a computer, to investigate three-dimensional tissue morphometry in biopsied iliac bone specimens from 20 female patients with femoral neck fractures. The 20 fracture patients were divided into two groups according to age: group I, patients below 70 years of age (n=10) and group II, patient 70 years of age or more (n=10). Five patients who also underwent iliac bone biopsy but who did not have fractures served as the control group. We found that the ilium in group I patients was composed of many small thin trabecular structures, while the ilium in group II was composed of only a few broad trabecular structures. The three-dimensional Euler number was small in osteoporosis, suggesting that trabecular connectivity was also diminished and the fractal dimension decreased. This indicated that the trabecular structure had become irregular. These findings indicate that the number of trabeculae appeared to decrease with trabecular blocking due to osteoporotic changes, and, simultaneously with this phenomenon, the which of the individual trabeculae seemed to become thicker in accordance with bone adaptation to mechanical stress.A summary of this paper was reported at the 9th Annual Orthopaedic Research Meeting of the Japanese Orthopaedics Association (October, 1994), and the 3rd Study Meeting of the Japanese Society of Osteoporosis (October, 1994).     

Electromagnetic stimulation of bone repair: a histomorphometric study

The effect of pulsing electromagnetic fields (PEMFs) on bone repair was studied in principal metacarpal bones of eight adult male horses: Six horses were treated with PEMFs, and two horses were untreated. In treated horses, Helmholtz coils were applied during a 60-day period to the left metacarpal bones, bored with eight holes of equal diameter and depth, from the middiaphysis toward the distal metaphysis. Eight equal holes bored in the right metacarpal, surrounded by unactivated Helmholtz coils, were taken as controls. The two untreated horses were taken as additional control. The results of computer-assisted histomorphometric analysis indicate that (a) in diaphyseal levels, the amount of bone formed during 60 days is significantly greater (p less than 0.01) in PEMF-treated holes than in contralateral ones and those in control horses; (b) in metaphyseal levels, PEMF-treated holes are sometimes more closed, sometimes less, as compared with contralateral holes and those in control horses; in any case the statistical analysis indicates that the symmetry in the rate of hole repair, found between the two antimeres of control horses, is not appreciable at metaphyseal levels also; (c) there was no statistically significant difference between untreated holes in PEMF-treated horses and holes in control horses, neither at diaphyseal nor at metaphyseal levels. These preliminary findings indicate that PEMFs at low frequency influence the process of bone repair on both diaphysis and metaphysis, and seem to improve the process of bone repair in skeletal regions normally having a lower osteogenetic activity, i.e., in diaphyses as against metaphyses.     

A histomorphometric determination of iliac bone structure and remodeling in obese subjects

Quantitative histomorphometric analyses of iliac crest biopsies were performed after tetracycline double labeling in 24 patients with morbid obesity and in 30 age- and sex-matched controls. The amount and structure of bone were determined from measurements of total biopsy length, fractional length of medullary space, fractional trabecular bone volume, trabecular thickness, and the intertrabecular distance. Static and dynamic variables of bone resorption and formation were determined, and the balance of the BMU level was estimated from final resorption depth and mean wall thickness of trabecular structural units. In the obese patients the total biopsy length was increased, with a normal proportion of medullary space to total biopsy length. The mean fractional trabecular bone volume was reduced due to an increased distance between trabeculae of normal mean thickness. The total biopsy length in the obese patients was found to be positively related to the intertrabecular distance and inversely related to the fractional trabecular bone volume. The remaining histomorphometric variables describing bone formation rate at tissue, BMU, and cellular levels, the amount of bone formed, the mineralization process, mineralization lag time, bone resorption, and the balance between resorption and formation were all normal in the obese group.     

Structural and histomorphometric studies of iliac crest trabecular and cortical bone in autosomal dominant osteopetrosis: a study of two radiological types

Cylindrical iliac crest biopsies were obtained from 16 patients with autosomal dominant osteopetrosis after intravital double labeling with tetracycline, and compared with normal age- and sex-matched controls. Ten patients had the radiological type I (5 women, 5 men, aged 17-62 years, mean 42) characterized by diffuse, symmetrical osteosclerosis and enlarged thickness of the cranial vault. Six patients had type II (2 women, 4 men, aged 22-44 years, mean 36), where "Rugger Jersey Spine" and endobone are characteristic findings. Structural studies of cortical and trabecular bone were performed, and trabecular bone resorption and formation rates were studied using dynamic histomorphometry. The total biopsy length (C. Wi) were increased in type I (p less than 0.05), and unchanged in type II. Both types showed increased cortical width (Ct. Wi) (p less than 0.01 and p less than 0.05, respectively), and decreased fractional width of cancellous bone (Cn.Wi/C.Wi) (p less than 0.01 and p less than 0.05). The fractional trabecular bone volume (BV/TV) and trabecular thickness (Tb. Th) were both significantly increased in type I (p less than 0.05), while resorptive and formative indices of trabecular bone remodeling were normal. No difference was found in trabecular bone balance, which was slightly positive in both patients and controls. In type II osteopetrosis the eroded surfaces (OS/BS) were significantly increased (p less than 0.01), as was the total resorptive period RP) (p less than 0.05). The resorption depth (R.D.) was normal, while the resorption rate (MRR) was insignificantly decreased. Many big multinucleated osteoclasts were seen in this type suggesting defective resorptive function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Normative data on mineralization density distribution in iliac bone biopsies of children, adolescents and young adults

Bone mineralization density distribution (BMDD) as assessed by quantitative backscattered electron imaging (qBEI) in iliac crest bone biopsies has become in the last years a powerful diagnostic tool to evaluate the effect of metabolic bone diseases and/or therapeutic interventions on the mineralization status of the bone material. However until now, normative reference data are only available for adults. The aim of the present study is to close this gap and establish normative data from children and compare them with reference BMDD data of adults.qBEI analyses were performed on bone samples from 54 individuals between 1.5 and 23 years without metabolic bone diseases, which were previously used as study population to establish normative histomorphometric standards.In the trabecular compartment, none of the BMDD parameters showed a significant correlation with age. The BMDD was shifted towards lower mineralization density (CaMean − 5.6%, p < 0.0001; CaPeak − 5.6%, p < 0.0001; CaLow + 39.0% p < 0.001; CaHigh − 80.7%, p < 0.001) and the inter-individual variation was higher compared to the adult population.The cortices appeared to be markedly less mineralized (CaMean − 3.1%, p < 0.0001) than cancellous bone due to higher amounts of low mineralized secondary bone. However, the cortical BMDD parameters showed a strong correlation (r = 0.38 to 0.85, with p < 0.001 to < 0.0001) with cancellous BMDD parameters.In conclusion, this study provides evidence that BMDD parameters in growing healthy subjects are relatively constant and that these data can be used as normative references in pediatrics osteology. The larger inter-individual variability compared to adults is most likely related to alterations of the bone turnover rate during growth.     

A histomorphometric study of cortical bone activity during increased weight-bearing exercise

To quantify cortical bone response to weight-bearing exercise, bone size, mineral content, and formation were measured at the femoral midshaft in swine. Bone formation was measured histomorphometrically on the periosteal, endosteal, and osteonal surfaces. Sedentary adult crossbred sows (3 years, 229 kg) were randomly assigned to basal (B, n = 6), control (C, n = 7), or trained (T, n = 7) groups. The basal and control groups did not exercise and were killed initially (B) or after 20 weeks (C). The trained group walked on a treadmill 20 minutes/day at 5 km/h and 5% grade, 5 days/week for 20 weeks. Bone length, area, or fat-free dry weight was not different with time (B versus C) or with training (C versus T). Periosteal modeling was stimulated by walking. Periosteal formation surface and mineral apposition rate (MAR) were greater in trained than control femora. No effects of walking were measured on the endosteal surface. Intracortical remodeling was not affected by walking. The number of labeled osteons (22.4 cm-2) was not different among groups, but osteonal MAR was greater in trained (1.18 microns/day) than control (0.96 mu/day) femora. Walking for 20 weeks in the previously sedentary sows was not a sufficient stimulus to create differences in gross measures of bone size or mineral content but did increase periosteal and intracortical MAR. The primary effect of increased exercise appeared to be osteoblast activation.     

Evaluation of the osteoclastic population in iliac crest biopsies from 36 normal subjects: a histoenzymologic and histomorphometric study

After histochemical staining of tartrate-resistant acid phosphatase (TRAP) activity, the total and active trabecular resorption surfaces and the number of osteoclasts were determined by histomorphometry on iliac crest biopsies from 36 healthy volunteers. The subjects were separated into three groups according to age and sex. Total trabecular resorption surface showed no significant variation in any group, but the fraction of active resorption surface was significantly higher in the older population. The number of TRAP cells per mm2 of section area, related to trabecular bone volume or surface, showed a significant increase in elderly subjects. The mean osteoclast interface was similar in all the groups. We found a significant decrease in resorption depth between young and old populations. These results are consistent with a reduced activity of bone-resorbing cells in advancing age. These normal values, established after histochemical identification of osteoclasts, may be applied for evaluating abnormal bone-resorbing cell activity in metabolic bone diseases.     

Effect of a five-week swimming program on rat bone: A histomorphometric study

Summary To specify the exercise-induced changes on different skeletal sites, the effect of a 5-week endurance swin training was studied in rats. Eighteen Lyon strain (Sprague-Dawley) 5-week old female rats were divided into nine sedentary and nine swimming rats. Each swim training session was increased by 15 minutes from 2–6 hours per day. A histomorphometric study was performed at the primary and secondary spongiosa of the distal femur and at the secondary spongiosa of lumbar and thoracic vertebral bodies. After training, bone loss was observed in the secondary spongiosa of lumbar vertebral bodies (24.7%) and in the primary spongiosa of distal femur (15.2%). A tendency to bone loss was also detected in the secondary spongiosa of distal femur (10.8%), whereas no change was detected in thoracic vertebral bodies. In secondary spongiosa, bone loss was accompanied with a thinning of trabeculae. Total eroded surfaces and osteoid surfaces were significantly decreased in the three studied skeletal sites, suggesting a decreased bone turnover. The decreased thickness of osteoid seams in both lumbar vertebrae and distal femur could mean that the osteoblastic activity has also been altered at the cell level, leading to thinning of trabeculae. Five-week swim training with such duration and intensity of exercise appears unable to increase bone volume in rats and, therefore, causes adverse effects. The three studied bones seemed to adapt differently to experimental conditions. The lack of ground reaction forces induced by water immersion might have contributed to the observed bone loss. Normal gravity would be an important cofactor in the osteogenic effects of exercise.     

Effects of caffeine and exercise on the development of bone: a densitometric and histomorphometric study in young Wistar rats.

High doses of caffeine will induce calcium loss and influence the normal development of bone, whereas the proper exercise has positive effects on bone metabolism. This study investigated the possible effects of exercise to antagonize the caffeine-induced impairment of bone development in young male Wistar rats. A total of 32 male rats (5 weeks old) were divided randomly into four groups: group 1 rats were fed caffeine; group 2 rats were prescribed an exercise program; group 3 rats were fed caffeine and prescribed an exercise program; and group 4 rats served as the control group. The caffeine was fed via the animals' dietary water and the dosage was 10 mg/100 g body weight per day, 3 days a week. The exercise program was carried out on a treadmill for 10 weeks (5 days/week, 1 h/day, 70% VO(2)max). Body weight was measured weekly. After sacrifice, the tibia length was measured and the tibia was processed for histomorphometric analysis. Bone mineral density was measured by dual-energy X-ray absorptiometer at three different sites of the tibia. In addition, the calcium content of the right femur was measured by atomic absorptiometry. The results showed that both exercise and caffeine significantly lowered the body weight gain. Rats fed with caffeine (groups 1 and 3) had a significantly longer tibia as compared with the non-caffeine-fed rats (groups 2 and 4) (p = 0.0149). The histomorphometry study showed that thickness of the growth plate in the proliferative zone, the hypertrophic zone, and total growth plate was greater in caffeine-fed groups than in non-caffeine-fed groups. The cell number in the proliferative zone was higher in the caffeine-fed groups. Area ratio of trabeculae in the primary spongiosa of rats in groups 1 and 2 were significantly greater than the control group. Caffeine feeding (groups 1 and 3) induced a lower area ratio of bone trabeculae in the secondary spongiosa, whereas exercise training (groups 2 and 3) increased the thickness of the trabeculae. The exercise program counteracted the negative effect of caffeine on the trabecular thickness, but did not correct the trabecular bone ratio. The bone mineral density (BMD) of the tibia was significantly lower in caffeine-fed rats, and the exercise program did not show any counteracting effect on the caffeine-induced BMD reduction. The calcium content assay showed that caffeine feeding decreased the weight and total calcium content of the femur. Again this exercise program did not counterbalance the negative effects of caffeine. In conclusion, high doses of caffeine seemed to stimulate the growth of long bone. However, it caused more serious negative effects on bone, including bone mineral loss, lower BMD, and lower calcium content. Exercise training at 70% VO(2)max had little antagonizing effect on caffeine-induced impairment of bone formation. Therefore, the best way to prevent caffeine-induced negative effects on bone development is to lower caffeine exposure.     

Pediatric solid organ transplantation and osteoporosis: a descriptive study on bone histomorphometric findings

Background

Organ transplantation may lead to secondary osteoporosis in children. This study characterized bone histomorphometric findings in pediatric solid organ transplant recipients who were assessed for suspected secondary osteoporosis.

Methods

Iliac crest biopsies were obtained from 19 children (7.6–18.8 years, 11 male) who had undergone kidney (n?=?6), liver (n?=?9), or heart (n?=?4) transplantation a median 4.6 years (range 0.6–16.3 years) earlier. All patients had received oral glucocorticoids at the time of the biopsy.

Results

Of the 19 patients, 21 % had sustained peripheral fractures and 58 % vertebral compression fractures. Nine children (47 %) had a lumbar spine BMD Z-score below ?2.0. Histomorphometric analyses showed low trabecular bone volume (< ?1.0 SD) in 6 children (32 %) and decreased trabecular thickness in 14 children (74 %). Seven children (37 %) had high bone turnover at biopsy, and low turnover was found in 6 children (32 %), 1 of whom had adynamic bone disease.

Conclusions

There was a great heterogeneity in the histological findings in different transplant groups, and the results were unpredictable using non-invasive methods. The observed changes in bone quality (i.e. abnormal turnover rate, thin trabeculae) rather than the actual loss of trabecular bone, might explain the increased fracture risk in pediatric solid organ transplant recipients.     

Application of histomorphometric methods to the study of bone repair.

Standardized methods for the histomorphometric assessment of bone are essential features of most studies of metabolic bone diseases and their treatments. These methodologies were developed to assess coupled remodeling, focusing primarily on osteoblasts and osteoclasts, the anabolic and catabolic rates of these cells, and structural features of mature bone. Research studies on bone healing and the development of new therapeutic approaches for the enhancement of bone repair also require a comprehensive understanding of the basic cellular and tissue level mechanisms that underlie these processes. However, the histological methods developed for metabolic bone disease studies are not completely suitable for studies of bone repair because they are based on assumptions that there is little variation in tissue composition within a sample of bone and not generally designed to quantify other types of tissues, such as cartilage, that contribute to bone healing. These techniques also do not provide tissue-based structural measurements that are relatable to the specific types of biomechanical and radiographic structural assessments that are used to determine rates of bone healing. These deficiencies in current histological approaches therefore point to the need to establish standardized criteria for the histomorphometric assessments that are specifically adapted for the study of bone repair in models of fracture healing and bone regeneration. In this Perspective, we outline what we believe to be the specific structural, tissue. and cellular aspects that need to be addressed to establish these standardized criteria for the histomorphometric assessment of bone repair. We present the specific technical considerations that need to be addressed to appropriately sample repair tissues to obtain statistically meaningful results and suggest specific procedures and definitions of nomenclatures for the application of this technology to bone repair. Finally, we present how aspects of histomorphometric measurements of bone repair can be related to biomechanical and radiographic imaging properties that functionally define rates of bone healing, and thus, how these tools can be used to provide corroborating data.     

Effects of growth hormone on bone modeling and remodeling in hypophysectomized young female rats: a bone histomorphometric study

Growth hormone (GH) deficiency causes decreased bone mineral density and osteoporosis, predisposing to fractures. We investigated the mechanism of action of GH on bone modeling and remodeling in hypophysectomized (HX) female rats. Thirty female Sprague–Dawley rats at age 2 months were divided into three groups with 10 rats each: control (CON) group, HX group, and HX + GH (3 mg/kg daily SC) group, for a 4-week study. Hypophysectomy resulted in cessation of bone growth and decrease in cancellous bone mass. Periosteal bone formation decreased and bone turnover rate of endocortical and trabecular surfaces increased as compared to the CON group. GH administration for 4 weeks restored weight gain and bone growth and mitigated decrease in bone density after hypophysectomy. However, trabecular bone mass in the proximal tibial metaphysis remained lower in group HX + GH than in group CON. Dynamic histomorphometric analysis showed that bone modeling of periosteal bone formation and growth plate elongation was significantly higher in group HX + GH than in group HX. New bone formed beneath the growth plate was predominately woven bone in group CON and group HX + GH. Bone remodeling and modeling–remodeling mixed modes in the endocortical and PTM sites were enhanced by GH administration; both bone formation and resorption activities were significantly higher than in group HX. In conclusion, GH administration to HX rats reactivated modeling activities in modeling predominant sites and increased new bone formation. GH administration also increases remodeling activities in remodeling predominant sites, giving limited net gain in the bone mass.     

Growth disturbance of the ilium after splitting the iliac apophysis and iliac crest bone harvesting in children: a retrospective study at the end of growth following unilateral Salter innominate osteotomy in 21 children.

The morphology of the iliac bone was assessed at the end of growth on AP x-rays of the pelvis in 21 children who had previously undergone unilateral pelvic osteotomy. The nonoperated side was used as a reference. There were 13 girls and 8 boys. Age at operation varied from 12 months to 12 years with a mean of 3 years and 10 months. The patients were distributed in 2 groups depending on their age at operation: before age 5 (group A, 16 cases) or after age 5 (group B, 5 cases). The mean age at follow-up was 15 years and 2 months (range 11-19 years). The end of pelvic growth was established by Risser stage IV. Distinct hypoplasia of the ilium due to premature growth arrest was observed in 16 cases: 12 in group A and 4 in group B. Other changes in the morphology of the ilium were noted, e.a. increased height of the ilium which was noted in 12 cases. The cosmetic prejudice was however minor, as compared with the radiological changes. In the authors' opinion, the alar hypoplasia was related to growth disturbances due to repeated splitting of the iliac apophysis. To prevent this complication the authors recommend avoiding the use of an electrocautery to incise the iliac apophysis and cutting the Kirschner wires so that their proximal ends lie within the subcutaneous fat, in order to avoid repeated splitting of the apophysis at the time of hardware removal.     

High and low density in the same bone: a study on children and adolescents with mild osteogenesis imperfecta

Children and adolescents with osteogenesis imperfecta (OI) generally have low bone mineral density (BMD) at the lumbar spine and hip. However, the effects of the disease on diaphyseal bone have not been well characterized, even though long-bone fractures are common in such patients. In this study on 42 fully mobile children and adolescents with mild OI (age 6-19 years; 17 girls), lumbar spine, radius (metaphysis and diaphysis) and second metacarpal (diaphysis) were analyzed using dual-energy X-ray absorptiometry, peripheral quantitative computed tomography and radiogrammetry, respectively. Bone mineral content at the lumbar spine, radial metaphysis and radial diaphysis was between 25% and 31% lower than in age-matched healthy children and adolescents. At the lumbar spine and radial metaphysis, bone size (as estimated from projection area and cross-sectional area, respectively) was normal or only slightly below the results expected for healthy individuals, whereas bone size was very small at the diaphyseal sites of the radius and the second metacarpal. Total volumetric BMD is defined as the ratio between bone mineral content and bone volume. Therefore, these differences in bone size between skeletal locations led to markedly discrepant results for total volumetric BMD. Total volumetric BMD was low at the lumbar spine (23% below result expected for healthy subjects of the same age) and the radial metaphysis (-15%) but elevated at the radial diaphysis (+25%; all differences to controls significant at P < 0.001). Despite high volumetric BMD, estimated bending strength at the radial diaphysis was very low. These results demonstrate that volumetric BMD can be abnormally high and low within the same bone in the same individual and highlight the fact that volumetric BMD at diaphyseal sites does not provide a good estimate of bone strength when bone size is abnormal.     

老年髋部骨折患者骨组织形态计量分析

目的通过骨组织形态计量对老年髋部骨折患者的骨量和骨结构异常进行研究。方法 25例患者均接受髂骨活检。 A组 14例,为老年髋部骨折组,其中男 6例 (A1组 ),年龄 (75.01± 7.15)岁;女 8例 (A2组 ),年龄 (69.85± 11.58)岁。 B组 11例,为对照组,其中男 5例,女 6例;年龄 (41.44± 3.87)岁。所取标本经甲基丙烯酸甲酯包埋、硬组织切片、甲苯胺蓝染色后行组织形态计量分析。结果 (1)A组的骨小梁体积、皮质骨宽度、骨小梁密度、骨小梁厚度、结点末端比显著低于对照组 (P< 0.01),而骨小梁间距则明显高于对照组 (P< 0.01)。 (2)A组中 2例女性患者的病理改变较为特殊,其骨量参数与对照组相近;结点末端比在对照组 95％可信度区间之外,而与本组其他患者相似。结论 (1)骨小梁连续性显著下降,而非骨量降低是部分骨转换增高的绝经后女性髋部骨折的重要内因。 (2)按骨量、骨结构 (骨小梁连续性 )和骨转换状况,老年髋部骨折患者的骨组织病理改变可以分为三型。     

Bone mastocytosis. A report of nine cases with a bone histomorphometric study.

Bone mastocytosis is characterized radiographically in some patients by diffuse osteosclerosis and in others by demineralization. The reason for these apparently conflicting bone features is unknown. Bone remodeling and marrow mastocytosis infiltration were studied in nine cases of mastocytosis with bone marrow involvement. Six men, ranging from 42 to 78 years of age, and three women, 43, 55, and 73 years old, comprised the series. Two patients had severe and diffuse osteosclerosis. Seven had diffuse demineralization, with crushed vertebrae in four, suggesting common osteoporosis. In three of the seven, cutaneous mastocytosis was absent. Bone biopsies were undecalcified and stained with toluidine blue. In the seven patients with demineralization, the number of marrow mastocytes was increased (154 +/- 24 versus 2 +/- 0.5/mm2 in normal postmenopausal osteoporosis). Mastocyte nodules covering 1-9% of the marrow area were present in all seven patients. These patients showed a significant increase in remodeling; bone formation rate was increased, coupled with a decrease in mean wall thickness. Concomitantly, osteoclast surfaces were increased, with an increased amount of bone resorbed. The two patients with diffuse osteosclerosis had a markedly different histology; mast cell infiltration was dramatically increased (mastocyte count greater than 1000/mm2) with diffuse marrow fibrosis. Bone volume was increased as well, and most of the bone was woven with an intratrabecular mineralization defect. High bone remodeling and decreased osteoblast activity can explain bone loss in mastocytosis with demineralization. Mastocytosis with osteosclerosis is characterized by a more extensive marrow mast-cell infiltration and fibrosis.     

Metabolic bone disease with and without osteomalacia after intestinal bypass surgery: a bone histomorphometric study

We performed iliac bone histomorphometry after in vivo double tetracycline labeling 3-14 years after intestinal bypass surgery for obesity in 21 patients, selected because of clinical suspicion of metabolic bone disease, and compared the results with those of 40 age-matched normal control subjects. Osteomalacia defined by rigorous kinetic criteria was found in six cases, histologic features of secondary hyperparathyroidism without significantly impaired mineralization in one case, and possible osteomalacia masked by impaired matrix synthesis in one case. In the patients with definite osteomalacia, nonfracture bone pain was more frequent, corrected plasma calcium lower, plasma alkaline phosphatase and magnesium higher, and secondary hyperparathyroidism more severe than in the other patients. In the patients without osteomalacia there was a 24.5% reduction in trabecular bone volume compared to the controls; in contrast to age-related bone loss and post-menopausal osteoporosis, this was due mainly to reduction in the thickness rather than the density of trabecular plates. About two-thirds of the reduction in trabecular thickness was due to reduction in interstitial bone thickness, representing the cumulative effect of increased depth of osteoclastic resorption cavities, probably due in part to secondary hyperparathyroidism. About one-third of the reduction in trabecular thickness was the result of reduced mean wall thickness, representing insufficient osteoblastic matrix synthesis, probably due in part to malabsorption of an unidentified nutrient necessary for normal bone health. Resorption indices were not increased at the time of the biopsy, but there were persistent defects in the recruitment and activity of osteoblasts. Clinically significant bone loss after intestinal shunt surgery, as in several other clinical situations, results from the combined effects of an unsustained increase in bone resorption and a sustained decrease in bone formation.     

Static histomorphometry of human iliac crest and vertebral trabecular bone: a comparative study.

We recently developed a new, rapid method for conducting static histomorphometry on large histologic sections. This method has now been applied on both iliac crest and lumbar vertebral bone to compare the age-related changes at these two skeletal sites and to investigate the correlation between the histomorphometric measures at the iliac crest and the vertebral body. The material comprised matched sets of unilateral transiliac crest bone biopsies and lumbar vertebral bodies (L-2) from 24 women (19-96 years) and 24 men (23-95 years) selected from a larger autopsy material. Three female subjects (80, 88, and 90 years) had a known vertebral fracture of L-2. The iliac crest biopsies and 9-mm-thick mediolateral slices of half the entire vertebral bodies were embedded in methylmetacrylate, stained with aniline blue, and scanned into a computer with a flatbed image scanner at a high resolution. With a custom-made computer program the following static histomorphometric measures were determined: trabecular bone volume; marrow and bone space star volume; node-strut analysis; trabecular bone pattern factor; trabecular thickness; trabecular number; trabecular separation; and anisotropy of bone and marrow phase. In addition, connectivity density was measured (ConnEulor method). The results showed that the age-related changes in the static histomorphometric measures are generally similar in the iliac crest and the vertebral body, and that these age-related changes are independent of gender. An exception, however, is connectivity density, where the age-related changes are similar for women and men in the vertebral body but significantly different in the iliac crest. Furthermore, the results showed that the histomorphometric measures were weakly intercorrelated between the iliac crest and the vertebral body, despite the generally similar pattern in age-related changes at these two skeletal sites. The highest correlation coefficient was found for trabecular separation (Tb.Sp; r = 0.63). Trabecular bone volume showed a correlation coefficient of r = 0.59. It is concluded that static histomorphometry performed on one skeletal site does not automatically predict static histomorphometric measures at another skeletal site. Therefore, it is recommended that static histomorphometry be performed at the skeletal site of interest-if at all possible.