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Biomedical subjects

C M Schnitzler

Publications and source records attributed to C M Schnitzler.

At least 19 recordsLinked to original sources

Hepatic osteodystrophy in rats results mainly from portasystemic shunting.

BACKGROUND AND AIMS: In chronic liver disease, bone disease frequently develops. The contributions of the different features of liver disease such as parenchymal inflammation, portal hypertension, and portasystemic shunting on bone metabolism have not been systematically studied. The aim of this study was to identify the features of liver disease contributing to bone disease using rat models. METHODS: Parenchymal liver disease was induced by carbon tetrachloride administration, portal hypertension by partial portal vein ligation, and portasystemic shunting by end to side anastomosis of the portal vein to the inferior vena cava. Normal and sham operated surgical animals served as controls. Serum calcium, 25-hydroxy vitamin D (25-OH vit D), and osteocalcin levels, and urinary deoxypyridinoline excretion were analysed. Testosterone and oestradiol levels were determined in male and female rats, respectively. Interleukin 1, interleukin 6, and tumour necrosis factor alpha (TNF-alpha) were determined in serum. Bone density was measured in all groups and in addition, in the surgical groups, histomorphometry was performed on undecalcified specimens of the proximal tibia. The calcium content of the femurs, removed at termination and ashed, was determined. RESULTS: Early parenchymal disease and portal hypertension did not affect bone metabolism or body mass. Portasystemic shunting increased bone resorption, decreased bone formation, bone density, and trabecular bone volume which were commensurate with a reduction in body mass. TNF-alpha levels were elevated and testosterone levels were low in male portasystemic shunted rats. CONCLUSIONS: Portasystemic shunting in the rat adversely affects bone metabolism as part of a generalised catabolic state where high TNF-alpha and low testosterone and 25-OH vit D levels may play a role.

Absorptiometry, Photon↗

Bone disease in African children with slipped capital femoral epiphysis: histomorphometry of iliac crest biopsies.

African teenagers with slipped capital femoral epiphysis (SCFE) not infrequently also have genu valgum (knock-knee). Because we had previously demonstrated metabolic bone disease attributable to dietary calcium deficiency in black teenagers with genu valgum, we examined 29 black teenagers (15 male, 14 female) with SCFE for metabolic bone disease. Each patient had an iliac crest bone biopsy taken (after double tetracycline labeling) for routine histomorphometry, and blood and urine samples for bone biochemistry. Spinal bone mineral density was measured in 13 patients. Compared to reported data, we found our patients to be sexually more immature, older, at least as obese, and to have more severe and more frequently bilateral hip disease. Eighty percent of the children took dairy products only once or twice a week or less frequently, and 37.9% had genu valgum. Compared with race- and age-matched South Africans, bone biopsies in our patients showed lower bone volume (BV/TV, p = 0.0003), wall thickness (p = 0.0002), and trabecular thickness (Tb.Th, p = 0.0002), and a tendency to greater trabecular spacing (Tb.Sp, p = 0.053). Lower osteoid volume (OV/BV, p = 0.0001), osteoid surface (OS/BS, p = 0.0001), osteoid thickness (O.Th, p = 0.0002), double labeled surface (dLS/BS, p = 0.029), and bone formation rate (BFR/BS, p = 0.037) suggested poorer bone forming capacity in our patients. No evidence of hyperparathyroid bone disease or osteomalacia was found. BV/TV was below the reference range (14.2%) in 65.5% of cases; these patients had lower values for Tb.Th (p = 0.037) and Tb.N (p = 0.0003), greater Tb.Sp (p = 0.0002), a tendency to lower adjusted apposition rate (Aj.AR, p = 0.057), and had had less frequent intake of dairy products than those with normal BV/TV (p = 0.024). Furthermore, months since menarche correlated with histomorphometric variables BV/TV (r = 0.667, p = 0.009), Tb.Th (r = 0.745, p = 0.002), Tb.Sp (r = -0.549, p = 0.042), O.Th (r = 0.784, p = 0.0009), and Aj.AR (r = 0.549, p = 0.042). The correlation between Tb.Th and spinal bone mineral content (r = 0.656, p = 0.015) suggests that the reduced trabecular thickness reflected a generalized bone condition. A greater than normal proportion of patients had spinal bone mineral density values below -1 standard deviation (SD) of the mean (osteopenia) (p = 0.001). Patients tested for parathyroid hormone and 25-hydroxyvitamin D levels were found to have normal values. Parathyroid hormone correlated with Aj.AR (r = 0.661, p = 0.038) and serum phosphorus (r = -0.764, p = 0.010). We conclude that sexual immaturity and possibly past dietary calcium deficiency contributed to osteopenia, and that this, together with obesity, led to the development of more severe and more frequently bilateral SCFE in our patients than in reported series of black and white children.

Adolescent↗

Bone marrow composition and bone microarchitecture and turnover in blacks and whites.

We examined the relationship between bone histomorphometric variables versus marrow cellularity, marrow adiposity (among hemopoietic cells), and fatty degeneration (areas of only fat) of bone marrow in iliac crest bone samples from 98 normal black (n = 53) and white (n = 45) males and females. We found blacks to have greater marrow cellularity (p = 0.0001), less marrow adiposity (among hemopoietic cells, p = 0.0001), greater values for bone volume (p = 0.030), trabecular thickness (p = 0.002), and static bone turnover variables (osteoid volume, p = 0.001; osteoid surface, p = 0.001; osteoid thickness, p = 0.001; eroded surface, p = 0.0006) than whites. Marrow cellularity correlated positively with static bone turnover variables osteoid volume (r = 0.257, p = 0.011), osteoid surface (r = 0.265, p = 0.008), osteoid thickness (r = 0.217, p = 0.032), and eroded surface (r = 0.273, p = 0.007) when all 98 cases were analyzed together. These findings suggest that marrow cells may influence bone turnover. The extent of fatty degeneration, but not that of adipose tissue, increased with age in blacks (r = 0.476, p = 0.0003) and whites (r = 0.476, p = 0.001), as did bone loss. There was no racial difference in the extent of fatty degeneration. We conclude that the lesser extent of adiposity in blacks is a racial characteristic that is unaffected by aging, whereas fatty degeneration which may have partly occupied space vacated by bone loss, is an aging phenomenon, unrelated to race. Greater bone turnover in blacks may be expected to lead to more frequent renewal of fatigue-damaged bone, which together with sturdier bone structure may contribute to the lower fragility fracture rates in blacks.

Adult↗

Differences in mineral homeostasis, volumetric bone mass and femoral neck axis length in black and white South African women.

In South Africa, appendicular and lumbar spine bone mineral density (BMD) have been found to be similar in black and white women. However, femoral BMD has been found to be higher in black than in white women. Two different techniques were used to recalculate BMD to eliminate the possible confounding influence of ethnic differences in height on areal BMD measurements. Volumetric bone mineral apparent density (BMAD) values were calculated and bone mineral content (BMC) was corrected for body and bone size. This report analyses differences in BMD (corrected for height and weight), BMAD, BMC (corrected for body and bone size), femoral neck axis length (FNAL), mineral homeostasis and bone turnover (BT) in a group of 20 to 49-year-old premenopausal (105 whites and 74 blacks) and 45 to 64-year-old postmenopausal (50 whites and 65 blacks) female South African nurses. The corrected BMD and BMC findings were congruous, showing that both pre- and postmenopausal blacks and whites have similar distal radius and lumbar spine bone mass but that whites have lower femoral neck bone mass than blacks. In contrast, BMAD findings suggest that pre- and postmenopausal whites have lower bone mass at the lumbar spine and femoral neck than blacks but similar bone mass at the distal radius to blacks. There is a greater rate of decline in BMD in postmenopausal whites than in blacks. BMD at the femoral neck was 12.1% lower in premenopausal whites and 16.5% lower in postmenopausal whites than in blacks. There was a positive association between femoral neck BMD and weight in premenopausal blacks (R2 = 0.5, p = 0.0001) but not in whites. Blacks had shorter FNAL than whites in both the pre- and post-menopausal groups. Blacks had lower serum 25-hydroxyvitamin D (25-(OH)D) and higher 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels than whites. There were no ethnic differences in biochemical markers of bone formation (serum alkaline phosphatase and osteocalcin) or bone resorption (urine hydroxyproline and pyridinoline), or in dietary calcium intake in either the pre- or postmenopausal groups. In the postmenopausal group, whites had higher ionized serum calcium (p = 0.003), similar serum albumin, lower serum parathyroid hormone (p = 0.003) and higher urinary calcium excretion (p = 0.0001) than blacks. These results suggest that the higher peak femoral neck BMD in South African blacks than in whites might be determined by greater weight-bearing in blacks and that the significantly lower femoral neck BMD in postmenopausal whites than in blacks is determined by lower peak femoral neck BMD and a faster postmenopausal decline in BMD in whites. The higher incidence of femoral neck fractures in South African whites than in blacks is probably determined by the lower femoral neck BMD and longer FNAL in whites. The greater rate of decline in BMD in postmenopausal whites than in blacks is associated with an increase in urinary calcium excretion in whites. Measurement of biochemical markers of BT has not contributed to the understanding of ethnic differences in BMD and skeletal metabolism in our subjects.

Adult↗

Fewer bone histomorphometric abnormalities with intermittent than with continuous slow-release sodium fluoride therapy.

To help resolve the uncertainty whether sodium fluoride (NaF) therapy should be given intermittently or continuously, we examined iliac crest bone biopsies (before and after treatment) and fragility fracture rates in 35 intermittently treated (group I) and 69 continuously treated (group C) patients; all received calcium. The following statistically significant results were obtained. Reduction in vertebral fracture rate was similar in the two groups. Trabecular thickness and the structurally more important mineralized thickness increased only in group I. Group I also accumulated less excess osteoid (surface, volume). Mean osteoid thickness did not change in either group because of a bimodal distribution of wide seams with osteoblasts and double tetracycline labels, and thin seams without osteoblasts or labels. Osteoid was lamellar. Osteoid in abnormal sites (within bone marrow or bone, or around osteocytes) was found less frequently in group I. Adjusted apposition rate declined and mineralization lag time increased in both groups because of extended unlabelled osteoid seams. Erosion surface increased only in group C. Hook and/or tunnel erosion was seen less frequently in group I; it was closely associated with osteoid in abnormal sites and correlated with osteoid surface. Extended osteoid surface may have forced osteoclasts to hollow out trabeculae, leaving the empty osteoid shell in marrow. Excess osteoid volume and eroded surface and osteoid and erosion in abnormal sites correlated with bone fragility in group C. We conclude that intermittent therapy is to be preferred because it (1) increased mineralized trabecular thickness, (2) did not cause excessive osteoid accumulation and erosion, (3) showed less osteoid and erosion in abnormal sites and (4) led to a similar reduction in the vertebral fracture rate as did continuous treatment. The question of whether intermittency of therapy has some other effect independent of the cumulative dose of fluoride administered cannot be answered by this study.

Adult↗

Bone structure and turnover in the distal radius and iliac crest: a histomorphometric study.

In bone grafting procedures of the wrist, the distal radius would be a more convenient graft donor site than the conventionally used iliac crest. We compared tetracycline-labeled bone biopsies from these two sites in 18 white patients (12 males, 6 females, aged 26-66 years) undergoing bone grafting procedures of the wrist. Fourteen had had previous trauma, 1 osteonecrosis of the lunate, 2 mild rheumatoid arthritis, and 1 a brachial plexus palsy. The specimens were processed undecalcified and examined by routine histomorphometry for bone structure, static and dynamic bone turnover variables, and marrow cellularity. We found that bone from the distal radius had thinner cortices (p = 0.0001), lower bone volume (p = 0.01), thinner trabeculae (p = 0.029), greater trabecular separation (p = 0.015), and lower wall thickness (p = 0.0001), marrow cellularity (p = 0.0001), osteoid volume (p = 0.01), osteoid surface (p = 0.02), osteoid thickness (p = 0.0002), osteoblast surface (p = 0.001), eroded surface (p = 0.01), osteoclast surface (p = 0.012), mineral apposition rate (p = 0.0002), double-labeled surface (p = 0.0005), single-labeled surface (p = 0.006), bone formation rate (p = 0.0005), adjusted apposition rate (p = 0.0001), longer mineralization lag time (p = 0.012), and greater activation frequency (p = 0.003). Prolonged mineralization lag time in the radius was associated with thin osteoid seams and low adjusted apposition rates and was therefore attributable to a low level of osteoblast activity rather than to osteomalacia. We conclude that bone from the distal radius was structurally inferior to and had lower turnover than the iliac crest bone. We suggest that where a graft has to provide immediate structural integrity, the iliac crest is the preferred donor site. However, where bone graft is to be compacted into a small cavitary defect, distal radial bone may be an adequate alternative. A clinical study is needed to confirm this assumption.

Adult↗

Ethnic differences in bone density in female South African nurses.

In the United States, the higher prevalence of osteoporosis and the higher incidence of fractures in whites than in blacks may be attributed to the finding of lower bone density (BD) in both white children and adults. In South Africa, osteoporosis and fractures also occur more frequently in whites than in blacks. Appendicular BD has been found to be similar in black and white children in South Africa, but there is little information available on BD of adults in South Africa. This cross-sectional study aimed to assess changes in BD with age in adult females in South Africa and to assess possible differences in peak BD and in the rate of postmenopausal bone loss between blacks and whites. Data for 180 black and 184 white female nurses aged 20-64 years were analyzed. The distal radius bone density (RBD) was measured by single photon absorptiometry. The lumbar spine bone density (SBD) and the femur bone density (FBD) were measured by dual-energy X-ray absorptiometry. Blacks were shorter than whites (p = 0.0001), and blacks' weight, body mass index, and skinfold thickness increased with age. Peak SBD and RBD were similar in blacks and whites, but peak FBD was higher in blacks (p = 0.0001). This ethnic difference in peak FBD became apparent in the fourth decade. Peak FBD was similar in black and white subjects with normal body mass indices (p = 0.09), but in overweight subjects peak FBD was higher in blacks than in whites (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Metabolic bone disease in black teenagers with genu valgum or varum without radiologic rickets: a bone histomorphometric study.

Calcium deficiency in black (African) children can cause rickets and osteomalacia with severe limb deformities. It is not known whether black teenagers with genu valgum or varum but without radiologic rickets suffer from a related disorder. To examine this question we studied 26 such patients by iliac crest bone biopsy and serum and urine biochemistry: 12 patients (46%) had osteopenia with normal or low bone turnover, 5 (19%) mildly increased bone turnover, 4 (15%) histologic hyperparathyroidism, 2 (8%) preosteomalacia, and 3 (12%) osteomalacia (with features of hyperparathyroidism). Radiographs did not reflect the severity of the bone disease. Serum calcium levels correlated inversely with eroded mineralized surface (p < 0.001), osteoid surface (p < 0.01), osteoid thickness (p < 0.001), mineralization lag time (p < 0.001), and 1,25-(OH)2 vitamin D (p < 0.005), and 1,25-(OH)2 vitamin D correlated positively with osteoid surface (p < 0.05), osteoid thickness (p < 0.05), osteoid volume (p < 0.01), eroded surface (p < 0.05), and eroded mineralized surface (p < 0.0005). Tubular reabsorption of phosphate and 25-OH vitamin D levels were normal, and 1,25-(OH)2 vitamin D levels were normal to high. This suggests that calcium deficiency may have caused the increase in bone turnover and the mineralization defects. The most severe osteomalacia was found in males aged 16-19 years. We cannot explain the cause of the osteopenia. We conclude that all patients had bone disease.

Adolescent↗

Osteoporosis in African hemosiderosis: role of alcohol and iron.

This paper aims to examine the relative contributions made by alcohol and iron overload and hypovitaminosis C to the osteoporosis associated with African hemosiderosis. To characterize this bone disorder, we examined double-tetracycline-labeled iliac crest bone biopsies and serum biochemistry in 53 black male drinkers, 38 with (Fe+) and 15 without (Fe-) iron overload, and in controls. We reasoned that abnormalities found in both patient groups were likely to be caused by alcohol abuse and those found only in the Fe+ group to be caused by iron overload and hypovitaminosis C (iron/C-). The patient groups differed only with respect to greater erosion depth (p < 0.05) and abnormal markers of iron overload in the Fe+ group. Ascorbic acid levels were lower in the Fe+ group than in controls (p < 0.001). Bone volume and trabecular thickness were significantly lower in both patient groups compared with controls and therefore likely caused by alcohol. There were no positive correlations between formation and erosion variables in either patient group, which suggests uncoupling of formation from erosion, possibly as a result of alcohol abuse. Prolonged mineralization lag time associated with thin osteoid seams was found in 32% of patients, affecting both groups. This rules out osteomalacia and suggests osteoblast dysfunction, probably caused by alcohol. The number of iron granules in the marrow correlated with erosion depth (r = 0.373, p < 0.01), trabecular number (r = -0.295, p < 0.05), and trabecular separation (r = 0.347, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Histomorphometry of iliac crest trabecular bone in adult male baboons in captivity.

Data in the literature on bone histomorphometry in the baboon are scant. This study provides data from analysis of trabecular bone of the iliac crest of 16 adult male chacma baboons (Papio ursinus) in captivity. Five animals were young adults judging by the presence of growth cartilage in the iliac crest biopsy. Bone volume resembled that in humans, but trabeculae were thinner and more closely spaced. Bone turnover appeared somewhat lower than in humans. Coupling of resorption and formation was excellent as judged by cellular and kinetic variables; erosion surface was an unreliable indicator of ongoing coupling. The similarities between human and baboon trabecular bone make the baboon suited for the study of microstructure and bone turnover of trabecular bone with relevance to humans.

Animals↗

Comparison of the radiographic vertebral trabecular pattern with the vertebral fracture prevalence and spinal bone density.

Spinal bone densitometry allows accurate and precise measurement of the severity of bone loss. Where densitometry is not yet available medical practitioners have to continue to rely on clinical radiography. Since the grey levels of the radiographic image are highly inaccurate we studied the radiographic vertebral trabecular pattern for its suitability as a semiquantitative assessment of vertebral bone loss. We defined four vertebral trabecular pattern indices (VTPI 4 = normal, VTPI 1 = severe bone loss) and tested these for correlations with the prevalence of vertebral fractures, and with spinal and hip bone mineral density measured by dual-energy X-ray absorptiometry (DXA). We found negative correlations between VTPI and the percentage of patients with vertebral fractures (p = 0.0001), between VTPI and the number of vertebral fractures per patient (r = 0.606, p = 0.001) and between VTPI and the severity of vertebral fractures, and a positive correlation between VTPI and spinal (r2 = 0.556, p = 0.0001) and hip DXA values (r2 = 0.315, p = 0.0001). We conclude that the vertebral trabecular pattern index can be used to assess the severity of spinal bone loss when a bone densitometer is not available.

Absorptiometry, Photon↗

Bone quality: a determinant for certain risk factors for bone fragility.

Low bone quantity alone is insufficient cause for fragility fractures. This paper examines the role of bone quality in the fracture risk associated with age, sex, and race. Aspects of bone quality to be considered are bone architecture, matrix, mineralization, and fatigue damage. The trabecular network becomes progressively disconnected and weaker with age. Death of old osteocytes leads to hypermineralization and brittleness of bone. The stability of bone collagen declines with age, and unremodeled bone accumulates fatigue damage. The lower bone fragility rates in males than in females may be due to a combination of the larger male skeleton, greater cortical bone density after age 60 years, and greater bone turnover which would replace fatigue damaged bone. Fragility fracture rates in American and African blacks are lower than in whites, bone mineral density (BMD) is greater in American but not in African blacks (except for hip BMD), and American blacks have lower and African blacks higher bone turnover compared to whites. In South African blacks, trabeculae are thicker and better connected and trabecular bone undergoes less destructive age changes than in whites. To reconcile the disparate findings in American and African blacks we suggest that both groups have a genetic tendency to greater BMD than whites; American blacks realize this potential and African blacks do not, possibly because of calcium deficiency. Consequent high turnover removes fatigue damage and so improves bone quality. Weight-bearing activity in African blacks may be responsible for good hip bone density and thick trabeculae.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bone histomorphometry of the iliac crest, and spinal fracture prevalence in atrophic and hypertrophic osteoarthritis of the hip.

While some authors report high bone density in osteoarthritis (OA), surgical experience with total hip arthroplasty (THA) for primary OA suggests the existence of osteoporotic subsets of patients. To identify these we analysed 107 iliac crest bone biopsies, taken at THA, by routine histomorphometry for trabecular structural and bone turnover features, and examined radiographs of the spine for vertebral fractures. Patients were grouped by hip osteophyte size (none, atrophic; small, hypotrophic; moderate, supertrophic; large, hypertrophic OA), and by major architectural disorganization of the hip (hip joint destruction, protrusio). We found hip joint destruction to be 3 times more common in atrophic than in supertrophic and hypertrophic OA (p less than 0.05). Overall, the OA patients had lower bone volume (p less than 0.05) and thinner trabeculae (p less than 0.05) than controls. Worst affected were patients with hip joint destruction and with protrusio: they also had fewer and more widely spaced trabeculae than controls (p less than 0.05). The spinal fracture prevalence was highest in patients with hip joint destruction (higher than in the general population), intermediate in those with protrusio or atrophic OA, and lowest in patients with supertrophic or hypertrophic OA. We conclude that OA hip patients with joint destruction or protrusio have a high prevalence of generalized osteoporosis, and that the larger the hip osteophytes, the lower is the prevalence of generalized osteoporosis. Our findings suggest that the generalized bone status may influence the outcome of OA of the hip.

Age Factors↗

Skeletal manifestations of primary oxalosis.

We describe the clinical, radiographic and histological features of skeletal involvement in four patients with end-stage renal failure due to primary oxalosis. The clinical features were unrelenting bone pain, and in two patients multiple fractures. Radiographic features were, in chronological order: (1) radiodense metaphyses and other red marrow bone; (2) cortical defects in metaphyses; (3) spontaneous fracture-separations of epiphyses of long limb bones which healed poorly. The fractures occurred through crystal deposits, and fracture displacement was associated with extrusion of crystalline material from bone. On histological examination crystals were found to replace metaphyseal bone. Pericrystalline giant cell granulomata replaced bone marrow. Erosion surfaces near granulomas were increased. Subperiosteal and intra-osseous tophi of calcium oxalate were seen. Calcium oxalate appears to precipitate with greater facility than does physiological mineral. Bone showed the features of mixed uraemic osteodystrophy in all four patients. We conclude that: (1) the fractures occurred through heavy crystal deposits; (2) ununited fractures and intra-osseous and subperiosteal tophi contributed to the pain; (3) spontaneous fractures are of poor prognostic significance. We recommend that unstable fractures be internally fixed.

Adolescent↗

Iliac bone biopsies at the time of periarticular stress fractures during fluoride therapy: comparison with pretreatment biopsies.

We attempted to establish whether systemic changes in trabecular bone explain the development of stress fractures in the lower limbs during fluoride therapy for osteoporosis. To this end we compared transiliac bone biopsies obtained before treatment with those taken around the time of stress fractures after 14.3 +/- 10.9 (SD) months of therapy in six patients (group A). Biopsies from a comparable group of six patients without stress fractures at the time of the second biopsy (after 11.9 +/- 2.7 months of treatment) served for comparison (group B). The biopsies were processed undecalcified and examined by routine histomorphometry. The second biopsies did not show any significant improvement in mean bone volume or trabecular architecture. Although the second biopsies in group A had increased erosion surfaces (p less than 0.05) and greater osteoid volume (p less than 0.05), group B biopsies showed no difference in erosion surfaces but an increase in all osteoid parameters: osteoid volume (p less than 0.05), osteoid surface (p less than 0.05), and osteoid seam thickness (p less than 0.01). We reached the following conclusions: (1) the combination of increased erosion and replacement of removed bone by as yet unmineralized osteoid in the stress fracture group must have weakened bone and allowed the development of stress fractures. (2) Stress fracture patients may have mounted a less vigorous osteoblast response to fluoride than non-stress fracture patients. Under these conditions microfractures are likely to heal poorly and propagate to develop into full stress fractures. (3) Renal failure is a contraindication to fluoride therapy.

Biopsy↗

Risk factors for the development of stress fractures during fluoride therapy for osteoporosis.

We attempted to identify risk factors for the development of lower limb stress fractures during fluoride therapy for osteoporosis (OP). We compared 18 patients who developed 41 such fractures (26 periarticular, 6 femoral neck, 5 long bone shaft, 1 greater trochanter and 3 pubic rami fractures) during fluoride therapy, with 24 similarly treated patients who did not develop stress fractures. Treatment consisted of sodium fluoride 0.99 mg/kg per day, elemental calcium 1 g/day, and vitamin D. We obtained a previous fracture history, annual radiographs of the spine (fractures), hands (metacarpal cortical index, MCI) and pelvis (Singh index, femoral cortical index), three-monthly serum fluoride and alkaline phosphatase levels, and pretreatment transiliac bone biopsies (routine histomorphometry). The stress fracture group was found to have, before treatment: lower MCI (p less than 0.05), lower trabecular bone volume (p less than 0.05), a lower number of trabeculae (p less than 0.05), greater trabecular separation (p less than 0.05), less extensive eroded surfaces (p less than 0.05), a lower double/single tetracycline label ratio (p less than 0.05); and during treatment: more new spinal fractures (p less than 0.05) and higher serum alkaline phosphatase levels (p less than 0.01). We conclude that stress fracture patients had more severe trabecular and cortical OP and possibly a poorer bone-forming capacity before therapy than patients without stress fractures. We suspect that fluoride therapy may temporarily further weaken bone and so lead to stress fractures in severely osteoporotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Histomorphometry of iliac crest bone in 346 normal black and white South African adults.

We examined undecalcified transiliac bone samples from 346 normal black and white South African adults (age range 21-83 years) by routine histomorphometry. The results were analysed for race-, age- and sex-dependent characteristics of trabecular microstructure (bone volume, trabecular thickness, trabecular number, trabecular separation) and static bone turnover variables (osteoid surface, osteoid volume, osteoid thickness, erosion surface). Trabecular thickness was greater in blacks than in whites, and bone volume was greater in black males, but not in black females, than in their white counterparts. Values for osteoid surface, volume and thickness, and for erosion surface were greater in blacks than in whites. Age-related changes were: a decline in bone volume in all race/sex groups; a decline in trabecular thickness in all groups except black males; a decline in trabecular number in all groups except black females; and a rise in trabecular separation in all groups except black females. There was an increase with age in osteoid surface in all groups except white males, in osteoid volume in all groups, and in erosion surface in blacks only. When correcting for age there were no sex-dependent differences in microstructure but values of some osteoid variables were greater in males than in females. If the greater osteoid and erosion values in blacks reflect greater bone turnover, then trabecular bone in blacks would be renewed more frequently, be subjected to fewer loading cycles and be less prone to fatigue failure. Blacks may thus have trabecular bone of better quality and sturdier microarchitecture. These features could contribute to the lower spontaneous fracture rate in blacks.

Adult↗

Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis.

Bone fragility during fluoride therapy for osteoporosis was observed in 24 (37.5%) of 64 patients treated with sodium fluoride, calcium, and vitamin D for 2.5 years who developed episodes of lower-limb pain during treatment. Eighteen (28%) of these patients had clinical and roentgenographic features of 41 stress fractures and 12 new spinal fractures. There were 26 periarticular, six femoral neck, three pubic rami, three tibia and fibula, one greater trochanter, and two subtrochanteric fractures. Vertebral fractures appeared first, then periarticular, then femoral neck, and lastly long-bone shaft fractures. All fractures were spontaneous in onset. The peripheral fracture rate during treatment was three times that in untreated osteoporosis. Roentgenograms must be repeated at intervals of three to four weeks before the pathognomonic callus becomes visible, and the diagnosis can be made. Trabecular stress fractures tend to occur in the first 18 months of treatment, and cortical stress fractures occur after 30 months of therapy.

Aged↗