Molecular cloning, purification and characterisation of myosin of human lymphatic filarial parasite Brugia malayi.

Global efforts have been made towards development of vaccine for prevention of lymphatic filariasis. However, lack of thorough knowledge about developmental biology and pathogenesis of filarial parasite restricts us from developing an effective vaccine. A limited number of immunodominant antigens of human lymphatic filariid Brugia malayi have been characterised; however, none of these recombinant antigens so far induced significant degree of protective immunity to challenge infection. In the present study, we identified a approximately 2.0 Kb cDNA clone by immunoscreening of cDNA library of adult female Brugia malayi. The nucleotide sequence of the identified clone showed 94.3% homology with C-terminal part of myosin heavy chain gene of Brugia malayi. This cDNA insert was sub-cloned into pET28b vector and expressed in BL21(DE3). The recombinant protein was purified to near homogeneity by immobilised metal affinity chromatography (IMAC) with yield of approximately 25 mg/l. The purified protein was recognised in western blot with anti-His tag antibody as also with the antibodies present in the sera of human W. bancrofti patients of all categories and infected/immunized rodent serum demonstrating its functional role. Recombinant myosin induced marked cellular immune response as observed by lymphoproliferation assay. The present findings demonstrate the usefulness of B. malayi recombinant myosin as vaccine candidate against human lymphatic filariasis.

A histomorphometric study of cortical bone of the iliac crest in patients treated with glucocorticoids.

The effects of glucocorticoids on cancellous bone remodeling and structure are well documented but there are no reported histomorphometric studies in human cortical bone in glucocorticoid-treated patients. We have performed a histomorphometric analysis of iliac crest cortical bone in 14 patients treated with glucocorticoids, 9 females and 5 males, aged 18 to 48 years (34.1 +/- 7 years) (mean +/- standard deviation [SD]). The underlying disease was cystic fibrosis in 8 patients; asthma 3; and nephrotic syndrome; Crohn disease and inflammatory pseudotumor of the liver in one patient each. Results were compared with an age-matched control group of 10 premenopausal women and 4 men aged 22 to 38 years (30.1 +/- 4.8 years) who were not, however matched for underlying disease. Cortical bone indices were assessed by image analysis. Cortical width and area were similar in the two groups. However, cortical porosity, Haversian canal number, and density were higher in patients treated with glucocorticoids compared with controls (8.4 +/- 8.9% vs. 5.1 +/- 3.9%; P = 0.03) (45.9 +/- 23.2 vs. 31.9 +/- 24.4; P =0.003) (13.7 +/- 9.4 vs. 6.7 +/- 3.3/mm2; P = 0.00005). Haversian canal area did not differ significantly between groups. The mean wall width of the osteons, bone formation rate (microm2/microm/day) and mineral apposition rate (microm/day) were lower in treated patients compared to controls (48.8 +/- 7.1 microm vs. 59.8 +/- 12.9 microm; P = 0.01) (0.056 +/- 0.040 vs. 0.095 +/- 0.058; P = 0.05) and (0.59 +/- 0.12 vs. 0.75 +/- 0.11; P = 0.002). The proportion of canals with an eroded surface was lower in the treated compared with the control group, although this difference was not statistically significant. These results demonstrate that cortical porosity is increased in patients treated with long-term glucocorticoid therapy, due mainly to an increase in the number rather than size of Haversian canals. This may be because of increased bone resorption during the early stages of glucocorticoid therapy, in combination with long-term impairment of bone formation. Effects of the underlying disease on bone remodeling may also contributed to these changes and could not be excluded in the present study; since control subjects were not matched in terms of disease status.

The effects of hormone replacement therapy on cortical bone in postmenopausal women. A histomorphometric study.

Investigations of the actions of estrogen on the skeleton have mainly focused on cancellous bone and there are no reported histomorphometric studies of the effects of oestrogen on cortical bone in humans. The aim of this study was to investigate the effects of both conventional hormone replacement therapy (HRT) and high-dose oestradiol on cortical bone in postmenopausal women. Transiliac biopsies were obtained from nine postmenopausal women aged 54-71 yr before and after 2 yr (mean, 23.5 months) of conventional HRT and in seven postmenopausal women aged 52-67 yr after long-term, high-dose oestradiol implant therapy (at least 14 yr). Indices of bone turnover, remodeling, and cortical structure were assessed by image analysis. Cortical width was highest in the women treated with high-dose oestrogen therapy (2.29 +/- 0.78 mm; mean +/- SD) and lowest in untreated women (1.36 +/- 0.60 mm; P=0.014). The proportion of canals with an eroded surface was significantly lower in the high-dose oestrogen group than in women before or after conventional HRT (3.03 +/- 3.7% vs. 11.1 +/- 7.1% and 10.5 +/- 8.6%; P=0.017 and 0.05, respectively). Bone formation rate (microm2/microm/day) in untreated women was significantly higher than in the high-dose oestrogen group (0.121 +/- 0.072 vs. 0.066 +/- 0.045, respectively; P=0.05), values in women treated with conventional HRT being intermediate. Our results provide the first histomorphometric evidence in postmenopausal women of dose-dependent oestrogen-induced suppression of bone turnover in iliac crest cortical bone. There was also a trend toward higher wall width with increasing dose of oestrogen, consistent with the previously reported anabolic effect in cancellous bone.

Increased femoral neck cancellous bone and connectivity in coxarthrosis (hip osteoarthritis).

Patients with coxarthrosis (cOA) have a reduced incidence of intracapsular femoral neck fracture, suggesting that cOA offers protection. The distribution of bone in the femoral neck was compared in cases of coxarthrosis and postmortem controls to assess the possibility that disease-associated changes might contribute to reduced fragility. Whole cross-section femoral neck biopsies were obtained from 17 patients with cOA and 22 age- and sex-matched cadaveric controls. Densitometry was performed using peripheral quantitated computed tomography (pQCT) and histomorphometry on 10-microm plastic-embedded sections. Cortical bone mass was not different between cases and controls (P > 0.23), but cancellous bone mass was increased by 75% in cOA (P = 0.014) and histomorphometric cancellous bone area by 71% (P < 0.0001). This was principally the result of an increase of apparent density (mass/vol) of cancellous bone (+45%, P = 0.001). Whereas cortical porosity was increased in the cases (P < 0.0001), trabecular width was also increased overall in the cases by 52% (P < 0.001), as was cancellous connectivity measured by strut analysis (P < 0.01). Where osteophytic bone was present (n = 9) there was a positive relationship between the amount of osteophyte and the percentage of cancellous area (P < 0.05). Since cancellous bone buttresses and stiffens the cortex so reducing the risk of buckling, the increased cancellous bone mass and connectivity seen in cases of cOA probably explain, at least in part, the ability of patients with cOA to resist intracapsular fracture of the femoral neck during a fall.

Reduced bone formation in UK Gulf War veterans: a bone histomorphometric study.

AIMS: Gulf War veterans report a high prevalence of musculoskeletal symptoms. The aim of this study was to establish whether there were abnormalities in bone turnover and remodelling in a group of symptomatic subjects who had served in the Gulf War. METHODS: Iliac crest bone biopsies were obtained from 17 Gulf War veterans who were seeking litigation and compared with those of 13 age and sex matched healthy controls. Bone histomorphometry was performed using image analysis. RESULTS: Cancellous bone area was significantly lower in Gulf War veterans than in control subjects (p = 0.027) and this was associated with a significantly reduced mineral apposition rate (p = 0.002), mean wall width (p < 0.0001), and bone formation rate at the tissue level (p < 0.0001). CONCLUSIONS: These results demonstrate that in this group of Gulf War veterans there was a significant reduction in bone formation at both the cellular and tissue level and this was associated with a reduction in cancellous bone area. The cause of these abnormalities is unknown but might be related to potentially harmful exposures during service in the Gulf War or to changes in life style as a result of chronic ill health. The clinical relevance of the observed reduction in bone formation remains to be established.

Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral density.

OBJECTIVE: To determine the effect of methotrexate (MTX) on bone mineral density (BMD) in rheumatoid arthritis (RA). METHODS: One hundred and sixteen non-steroid-treated RA subjects (90 women) were studied in a prospective, longitudinal, non-randomized study. Subjects started MTX (n=36) or sulphasalazine (n=23) or continued long-term (>5 yr) treatment with MTX (n=28) or other disease-modifying anti-rheumatic drugs (n=29). BMD was estimated at entry and after 1 yr. Markers of bone turnover were measured at entry and at 1 yr, and additionally at 3 and 6 months in those starting treatment. Bone biopsies were taken before and after MTX treatment in four subjects. The primary outcome was change in BMD Z score and secondary outcomes were changes in bone turnover markers and bone formation by histomorphometry. RESULTS: Univariate analysis of covariance found that MTX at baseline was associated with reduced BMD at the femoral neck. However, femoral neck BMD was also associated with radiological damage score for the hand. Multivariate analysis and discriminant analysis of the subset of post-menopausal women showed that reduced bone density associated with MTX was due to confounders such as disease activity. There was no adverse effect of MTX on bone turnover markers or on measures of bone formation in biopsies. CONCLUSIONS: No adverse effect of low-dose MTX (mean 10 mg/week) on bone formation in RA was found.

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.

Megakaryocyte population in human bone marrow increases with estrogen treatment: a role in bone remodeling?

Skeletal effects of conventional hormone replacement therapy (HRT) are predominately antiresorptive, while high doses of estrogen have anabolic effects. The mechanisms mediating these effects are unclear but may involve cells in the bone marrow. We have investigated the in vivo effects of estrogen on the megakaryocyte (MK) population in bone marrow in 10 postmenopausal women before and after 2 years of conventional HRT, in 11 women after long-term, high-dose estradiol therapy, and in 2 premenopausal and 4 postmenopausal women who had received no previous estrogen treatment. Transiliac crest biopsies were halved and either decalcified and paraffin wax embedded for immunolocalization studies or dehydrated and embedded in LR White resin for histology. MKs were identified morphologically, and the bone marrow cell population and MK number quantified by cell counting in a defined area of view (1 mm(2)) from 5 randomly selected fields of bone marrow. Compared with pretreatment values, significantly higher MK numbers were found after conventional HRT treatment (before treatment, mean +/- SEM; 7.3 +/- 1.1 vs. after treatment, 18.0 +/- 1.6/5 mm(2); p < 0.0001), while the greatest MK number was associated with long-term, high-dose estradiol treatment (32.8 +/- 2.1/5 mm(2); p < 0.0001). Total bone marrow cell number did not differ significantly between groups. Immunolocalization studies revealed more intense estrogen receptor (ER)beta expression in MKs in the high-dose estradiol-treated group but similar levels of weak ERalpha staining in MKs in the control and high-dose estrogen-treated groups. Positive immunoreactivity for transforming growth factor (TGF)beta1, 2, and 3 and TGFbeta receptor I, II, and III was detected in MKs, with more intense staining being demonstrated in the high-dose estradiol-treated group, particularly for TGFbeta2 and TGFbetaRI and II. Our results demonstrate an increase in the MK population in bone marrow from women treated with estrogen. The ability of MKs to express ERs and synthesise TGFbeta, a potent mitogen in osteoblast differentiation, suggests that these cells may play a role in mediating estrogen-induced effects on bone.

Bone structure in patients with low bone mineral density with or without vertebral fractures.

Vertebral fractures (VFX) are caused by low bone mass and microstructural deterioration of bone tissue. The latter is not well defined. We investigated bone structure in transiliac biopsy specimens from 88 volunteers. Biopsy specimens were obtained at baseline in the Multiple Outcomes of Raloxifene Evaluation trail, a prospective study in osteoporotic (BMD < or = -2.5 T score) postmenopausal women without or with VFX on standardized lateral spinal radiographs. Bone biopsy specimens were embedded in methylmethacrylate (MMA). Histomorphometry was done in 8 microns (U.S.A.) or 5 microns (Europe) Goldner stained sections. Vertebral fracture status (yes/no) was the outcome variable in logistic regression models adjusted for age and biopsy specimen origin (U.S.A. vs. Europe). Patients with and without VFX (26/62) were similar regarding age (69.2 +/- 5.2 years vs. 67.3 +/- 6.7 years), bone volume (BV/TV; 17.7 +/- 4.7% vs. 19.0 +/- 5.8%), and bone surface (BS/TV; 2.7 +/- 0.6 mm2/mm3 vs. 2.8 +/- 0.6 mm2/mm3). A lower cortical thickness (C.Th; 652 +/- 267 microns vs. 822 +/- 325 microns), total strut length (TSL; 826 +/- 226 microns/mm2 vs. 922 +/- 256 microns/mm2), node-to-loop (Nd-Lp) strut length (10.1 +/- 10.3% vs. 15.0 +/- 13.6%), together with a higher node-to-terminus (Nd-Tm) strut length (45.6 +/- 9.7% vs. 39.1 +/- 9.3%) were each associated with prevalent VFX (0.01 < p < 0.10). Differences in BV/TV did not explain these associations. In conclusion, cortical thinning and disruption of trabecular lattice are possible pathogenic mechanisms in patients with VFX.

Reduced bone formation after exposure to organophosphates.

Bone histomorphometric analysis in 24 agricultural workers with chronic organophosphate exposure showed significantly lower bone formation at tissue and cellular level than in healthy controls.

Bone remodeling and structure in postmenopausal women treated with long-term, high-dose estrogen therapy.

Conventional hormone replacement therapy preserves bone mass predominantly by reducing bone turnover but does not exert significant anabolic skeletal effects. In contrast, high doses of estrogen have been shown to increase bone formation in animals and we have recently reported high bone mineral density values in women treated long-term with estradiol implant therapy. The aim of this study was to investigate the mechanisms by which high doses of estrogen may increase bone mass in postmenopausal women. Iliac crest biopsies were obtained from 12 women who had received long-term treatment with estradiol implants (at least 14 years), on demand, following hysterectomy and bilateral salpingo-oophorectomy. Indices of bone turnover, remodeling balance and cancellous bone structure were assessed by image analysis and compared with those of premenopausal women. Mean wall width was significantly higher in women treated with estradiol therapy than in premenopausal women (44. 8 +/- 4.8 vs 38.8 +/- 2.8 mm; mean +/- SD; p = 0.001) and eroded cavity area was significantly lower in the implant-treated women (3612 +/- 956 vs 5418 +/- 1404 mm(2); p = 0.001). Bone formation rate at tissue level and activation frequency were lower in the women treated with implants, although the differences were not statistically significant. Indices of cancellous bone structure were generally similar between the two groups. These results provide the first direct evidence that high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women and indicate that these are achieved by stimulation of osteoblastic activity.

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 effect of training on the calcified zone of equine middle carpal articular cartilage.

Carpal osteochondral injury is frequently observed in strenuously trained horses. It is clear that the integrity of articular cartilage and subchondral bone are intimately related, although there is controversy about which component is the most important. Calcified cartilage provides the mechanical link between soft hyaline cartilage and stiff subchondral bone so it is essential to understand the tissue's response to exercise. Middle carpal calcified and uncalcified (hyaline) cartilage thickness was investigated in horses undergoing high- and low-intensity exercise. Twelve untrained horses (18-21 months) were paired, and randomly assigned to an exercise group. Group 1 underwent 19 weeks progressive high-intensity training on a high-speed treadmill. Group 2 underwent walking exercise only. Osteochondral specimens were obtained from 8 test sites per carpus immediately after euthanasia. Histomorphometric measurements of total cartilage, hyaline layer, and calcified zone thickness were obtained from decalcified and undecalcified samples. Mean +/- s.d. (micron) calcified cartilage thickness for dorsal cartilage from Group 1 was 271 +/- 73 and from Group 2 was 163 +/- 49; for palmar cartilage from Group 1 was 195 +/- 42 and Group 2 was 150 +/- 52. Group 1 horses had significantly thicker total cartilage (P < 0.0001) and calcified zone (P < 0.0001) than Group 2, but there was no difference in hyaline layer. Within each group all dorsal sites had thicker calcified cartilage (P < 0.003) than palmar sites, but no difference in hyaline or total cartilage. These findings indicate that high-intensity exercise leads to greater calcified zone depth without alteration in hyaline cartilage thickness, and that this response is maximal at sites that withstand high, intermittent loads. Increasing calcified cartilage thickness with exercise may maintain the articular surface stiffness gradient in the face of alterations in hyaline cartilage and/or subchondral bone stiffness.

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 postmenopausal 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.

Effects of hormone replacement therapy on cancellous bone microstructure in postmenopausal women.

Menopausal bone loss is associated with disruption of cancellous bone architecture which has adverse mechanical effects and is believed to be irreversible. The aim of this study was to examine the effects of long-term hormone replacement therapy on cancellous bone structure in women with postmenopausal osteoporosis. Iliac crest biopsies from 22 women with osteopenia or osteoporosis were obtained before and after hormone replacement therapy (mean duration 23.5 months). Cancellous bone architecture was assessed by strut analysis, trabecular bone pattern factor, and marrow star volume. Post-treatment biopsies showed no significant changes in any of the structural indices assessed. Our results suggest that hormone replacement therapy preserves existing cancellous bone structure but provide no evidence that this treatment is able to reverse structural disruption in women with postmenopausal osteopenia or osteoporosis.

Bone turnover in non-steroid treated rheumatoid arthritis.

OBJECTIVE: To examine whether changes in cancellous bone turnover and resorption cavity depth contribute to bone loss in patients with non-steroid treated rheumatoid arthritis. METHODS: Iliac crest biopsies were obtained from 37 patients with non-steroid treated rheumatoid arthritis, 13 male and 24 female, aged 37-71 years. Bone turnover and resorption cavity characteristics were quantitatively assessed using semiautomated computerised techniques. RESULTS: When compared with age- and sex-matched control values, there was a significant reduction in bone formation rate at tissue level and activation frequency (P < 0.001) in the patient group. The eroded perimeter, mean and maximum eroded depth and cavity area were also significantly reduced (P < 0.01, < 0.005, < 0.01 and < 0.005 respectively). CONCLUSION: These results demonstrate low bone turnover in non-steroid treated rheumatoid arthritis and indicate that the reduced bone mass in these patients is due mainly to a negative remodelling balance.

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.

Combined inter-observer and inter-method variation in bone histomorphometry.

Manual methods for the measurement of bone biopsies have largely been superseded by semi-automatic computerised techniques. Histomorphometrists often use control data obtained by other observers using different methods, thus combining inter-observer and inter-method variation. We have examined the combined effect of inter-method and inter-observer variation on measurements of bone area, osteoid perimeter, and osteoid width in iliac crest biopsies from healthy subjects, one observer using the manual grid system and the other using a semi-automated technique. Inter-observer and inter-method variation were independently determined, and the proportion of each expressed as a percentage of combined error. Our results indicate that the combination of inter-method and inter-observer variation causes significant differences in the values obtained for osteoid perimeter, whereas inter-method variation is mainly responsible for differences in osteoid width values; differences in bone area are largely due to inherent sampling variation. These variations indicate that caution is required when comparison is made with control data from other sources, especially if different techniques are employed.

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.

Quantitative microfocal radiography of children with renal osteodystrophy; comparison with laboratory and histological findings.

High definition microfocal radiography permitted the quantitative assessment of the radiographic features of renal osteodystrophy in the phalanges of 11 children in stable chronic renal failure, treated with phosphate binders for 1 year. The most consistent feature was subperiosteal cortical resorption, expressed as a ratio total length of resorbed subperiosteal bone/total length subperiosteal bone x 100. It was found that the extent of resorbed bone was significantly greater in the middle phalanx and on the ulnar surface of the phalanges. The radiological findings over the duration of the disease were compared with laboratory assessments and bone histomorphometry. The extent of the percentage of subperiosteal resorption at base line and its change during the study period correlated significantly with the level of serum parathyroid hormone levels and its change over the same period. No other significant correlations were found between radiographic features and laboratory assessments or with bone histomorphometry.