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Biomedical subjects

C M Schnitzler

Publications and source records attributed to C M Schnitzler.

At least 37 records · Page 2Linked to original sources

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↗

Regression with an ordered categorical response.

A survey on Mseleni joint disease in South Africa involved the scoring of pelvic X-rays of women to measure osteoporosis. The scores were ordinal by construction and ranged from 0 to 12. It is standard practice to use ordinary regression techniques with an ordinal response that has that many categories. We give evidence for these data that the constraints on the response result in a misleading regression analysis. McCullagh's proportional-odds model is designed specifically for the regression analysis of ordinal data. We demonstrate the technique on these data, and show how it fills the gap between ordinary regression and logistic regression (for discrete data with two categories). In addition, we demonstrate non-parametric versions of these models that do not make any linearity assumptions about the regression function.

Adolescent↗

Endemic skeletal fluorosis in children: hypocalcemia and the presence of renal resistance to parathyroid hormone.

Although endemic skeletal fluorosis has been reported in children, hypocalcemia has not been previously noted. In a prevalence study of 260 schoolchildren living in an endemic fluorosis area in South Africa (water fluoride content 8-12 ppm), hypocalcemia was documented in 23%. Furthermore in a separate study of nine children with skeletal symptoms due to endemic fluorosis, hypocalcemia was found in six. 1,25-Dihydroxyvitamin D levels were elevated in the seven children in whom it was measured. Parathyroid hormone (PTH) stimulation tests on admission revealed evidence of impaired phosphaturic responses, typical of acquired pseudohypoparathyroidism type II, and a direct correlation between serum calcium values and the degree of phosphaturia was noted. Repeat tests performed in two of the children after correction of the hypocalcemia by dietary means, revealed a return of normal renal responsiveness. Serum calcium values also correlated inversely with the degree of osteomalacia on iliac crest bone histomorphometry. It is suggested that low dietary calcium intakes might exacerbate the severity of the bone lesions in children living in areas of endemic fluorosis.

Adolescent↗

Bone induction in a composite allogeneic bone/alloplastic implant.

This study evaluated the morphogenetic properties of the bone matrix as a biological delivery system in a composite allogeneic bone/alloplastic implant placed in extraskeletal recipient sites in rats. Seventy-two allogeneic diaphyseal bone cylinders were chemosterilized to obtain autolyzed antigen-extracted allogeneic (AAA) bone and implanted in twenty 140- to 160-day-old rats. In 30 implants, porous hydroxyapatite biomatrix (HAB) was inserted into the AAA bone cylinders creating the composite implants. Serial sections from the specimens harvested at 23, 30, 45, 53, and 63 days showed that 84% of the AAA bone cylinders induced the differentiation of variable amounts of endochondral bone and that in 61% bone formed in the interior of the cylinders; 74% of the composite implants had no bone-inductive effect, recruiting instead macrophages and multinucleated giant cells at the HAB/mesenchymal interface. In all instances bone failed to form within the porous HAB or in proximity to the AAA bone matrix facing the interior of the cylinders. When present, bone formed only in localized areas within the matrix. Histologic analysis showed that high deposits of induced bone are correlated to high levels of matrix vascular invasion and mesenchymal cell aggregation. Within the limits of this study on rodents, the results suggest that the HAB inhibits and delays the local differentiation of induced bone in the composite implants.

Animals↗

Serum keratan sulfate levels in osteoarthritis patients.

Serum levels of keratan sulfate (KS), measured by an enzyme-linked immunosorbent-inhibition assay, were found to be significantly higher in 31 patients with hypertrophic osteoarthritis (OA) than those in 41 adults without joint disease. Seventy-seven percent of patients with OA, but only 12% of control subjects, had serum levels which were more than 1 SD above the mean of the control group. Following replacement of a single osteoarthritic hip joint, serum KS levels decreased, at first, in all patients. Subsequently, the concentration of serum KS progressively increased; 6 months following surgery, KS levels were similar or close to the preoperative levels in virtually all patients. The results suggest that patients with hypertrophic OA may have a generalized imbalance of cartilage proteoglycan metabolism. Measurements of serum KS are likely to prove most useful in studying this particular subset of patients with generalized OA.

Aged↗

Histomorphometric analysis of osteopenia associated with endemic osteoarthritis (Mseleni joint disease).

Mseleni Joint Disease (MJD), a polyarticular osteoarthritis of uncertain etiology is endemic among the Tonga-Zulu tribe. The traditional diet is deficient in calcium, and palm wine (2-4% alcohol) is drunk widely. Patients with MJD are reported to be more osteopenic than those without. Iliac bone biopsies of 19 arthritic patients were examined by routine histomorphometry and revealed decreased trabecular bone volume (p less than 0.0005), increased resorption surfaces (p less than 0.01), decreased bone formation rate at the BMU (p less than 0.01) level and increased mineralization lag time (p less than 0.01). Six of the 19 patients (31.6%) had features of osteomalacia and six (31.6%) signs of osteoblast failure. The most likely cause of the bone disorder is calcium deficiency, but inanition, inactivity and alcohol abuse may have contributed. Although the joint disorder may have contributed to the bone disorder, the converse is unlikely the case.

Adult↗

Serum biochemical and haematological markers of alcohol abuse in patients with femoral neck and intertrochanteric fractures.

Excessive alcohol intake causes bone loss. Alcohol abuse is a commonly associated disorder in femoral neck fractures in men, but little attention is given to such an association in women. Using serum biochemical and haematological markers (mean red cell volume MCV, gamma-glutamyl transpeptidase GGT, aspartate transaminase AST, uric acid UA and triglyceride TG) alcohol abuse was assessed in 14 men and 93 women with non-violent fractures of the hip. Abnormal elevations in one or more of the five test pairs known to correlate with increasing alcohol consumption (GGT/MCV, GGT/AST, AST/MCV, MCV/UA) were found in 7.1% of men, and 11.8% of women. When abnormal results in other test pairs were included the prevalence rose to 14.3% in men and 20.4% in women. These figures are higher than those reported for the general population of elderly people.

Adult↗

Osteopenia of the pelvis associated with Mseleni joint disease. Radiological aspects.

Mseleni joint disease, an endemic form of osteoarthritis (OA), is associated with osteopenia (OP). In a detailed investigation of the disorder, the degree of OP was assessed in 593 radiographs of the pelvis which were taken during surveys of four populations: rural blacks from Mseleni, rural blacks from Manguzi (a similar population to Mseleni), a black control group of rural Tswanas and a white control group from Johannesburg. Only females were included because the number of males in the rural populations was too small. The radiographic trabecular pattern was assessed at four sites: sacrum, ilium, pubis and ischium. Four grades were used: O = normal bone, 1 = minimal OP, 2 = definite OP, 3 = severe OP. The sum of the grades at the four sites made up the OP score for the individual. The OP scores increased with age in all groups, the age-specific mean OP scores did not differ in the non-OA subgroups of all four populations, and subgroups with OA had significantly higher age-specific mean OP scores than those without OA.

Adolescent↗

Proteoglycans of articular cartilage in Mseleni joint disease.

Femoral heads were resected from patients with Mseleni joint disease, and cartilage present in 'islands' on the articulating surfaces and over marginal osteophytes was removed for study. Some specimens were grown in short-term organ culture and labelled with sulphur-35. Proteoglycans present in the tissue, and newly synthesised macromolecules were extracted, purified and assessed. The results indicated that very few of the proteoglycans present or synthesised during culture were capable of aggregation with hyaluronate and that the average size of the macromolecules was smaller than normal. In addition a large proportion of the proteoglycans were very small in size and were thought to resemble a molecule found in immature articular cartilage. The response to degenerative disease was unusual and may be peculiar to the Mseleni condition.

Cartilage, Articular↗

Radiographic features of the spine in fluoride therapy for osteoporosis.

In the search for a simple method of assessing the therapeutic efficacy of sodium fluoride, a prospective study of vertebral radiography during such treatment was carried out. Treatment of osteoporosis with sodium fluoride, calcium and vitamin D was found to enhance the vertical markings of the vertebral trabecular pattern in 69% of patients. This response was graded 1 (failure), 2 (good) and 3 (excellent); Grade 2 or 3 was attained after a mean treatment period of 31.7 months. Subsequent analysis of the vertebral fracture rate revealed that new vertebral fractures had occurred only in patients with Grade 1 and not in those with Grade 2 or 3. We recommend that treatment should aim at increasing the vertebral trabecular pattern to Grade 2 or 3 and that the duration of therapy should be approximately 30 months.

Adult↗

Distinct types of hip disorder in Mseleni joint disease.

Painful arthropathy of the hips is common in the black population around Mseleni in northern Kwazulu. Despite considerable variability in clinical and radiographic appearance, the disorder has always been regarded as a single entity. This study addressed the possibility that 'Mseleni joint disease' embraces more than one condition. In a survey of 1659 people in the Manguzi Health Ward, 60 km north of Mseleni, 126 were reported to have hip pain and/or impaired walking ability; 92 of these subjects were examined radiographically. Osteo-arthritis (OA) of the hips was found in 33 cases, the prevalence increasing with age to over 16% in those aged over 60 years. In most cases the OA was associated with two distinct abnormalities: protrusio acetabuli, which affects mainly females and increases in frequency with age, and hip dysplasia, which has a constant frequency with age. The protrusio disorder is fairly common among women of other black populations and is attributed to environmental factors. The hip dysplasia is unique to the population around Manguzi; it is part of a generalized condition indistinguishable from multiple epiphyseal dysplasia, which is a known genetic disorder.

Acetabulum↗

Histomorphometric analysis of a calcaneal stress fracture: a possible complication of fluoride therapy for osteoporosis.

Pain and swelling of the large joints of the lower limbs occur in about 33% of patients receiving sodium fluoride, calcium, and vitamin D therapy. In a previous study we described radiographic and scintigraphic features suggesting that these symptoms are due to juxtaarticular stress fractures. We now report the histologic features of one such lesion in a calcaneum of a patient receiving fluoride, calcium, and 1 alpha-vitamin D therapy for postmenopausal osteoporosis. Bone biopsy after tetracycline double labeling showed a trabecular fissure fracture and large intratrabecular resorption cavities surrounded by microcallus. Comparison of the static and dynamic histomorphometric parameters in the calcaneum with those in the simultaneously taken iliac bone biopsy showed a marked regional acceleratory phenomenon in the calcaneum that we ascribe to the microfractures. It cannot be said with certainty whether the microfractures resulted from the osteoporosis, the vitamin D, or the sodium fluoride therapy.

Bone Resorption↗

Trabecular stress fractures during fluoride therapy for osteoporosis.

Joint pain and swelling in patients on fluoride therapy are generally attributed to rheumatic phenomena; however, their occurrence exclusively in the lower limbs suggests a mechanical cause. Eight patients receiving daily doses of sodium fluoride 1.09 mg/kg, elemental calcium 1 gm, and vitamin D 1000-2800 units for osteoporosis spontaneously developed 17 episodes of periarticular pain and swelling in the lower limbs. Radiographs taken within two weeks of the onset of pain were negative, but when repeated 4-6 weeks later showed features of healing stress fractures in the periarticular cancellous bone at the following sites: distal femur (2) proximal tibia (3), distal tibia (6), calcaneum (6). Bone scintigraphy was positive on five occasions, two before radiographic signs had appeared.

Aged↗

Bone changes after alcohol abuse.

In this study bone morphometric findings in 19 heavy or moderate drinkers are compared with those in 43 non-drinkers (22 non-osteoporotic patients with osteo-arthritis (OA) and 21 osteoporotic patients with femoral neck fractures (FNFs). Transiliac bone biopsy specimens were examined for assessment of trabecular bone volume and thickness, bone resorption and formation, osteoid seam length and width and the mineralization front by quantitative histomorphometry and microradiography. Trabecular bone volume and thickness were significantly diminished in the drinking group when compared with those in the 22 non-drinking patients with OA (P less than 0,005 and P less than 0,0001 respectively). Bone formation was significantly lower in the drinkers than in the OA group (P less than 0,0005), and bone resorption was significantly greater in the drinkers than in the OA (P less than 0,005) and FNF (P less than 0,01) groups. In heavy drinkers bone formation was significantly lower (P less than 0,05) than in moderate drinkers. The extent of the mineralization front was significantly lower in the drinking group than in the OA (P less than 0,005) and FNF (P less than 0,0005) groups. Osteoid seam length and width did not differ in the three groups. The presence of abnormal liver function test results did not significantly affect any of the parameters. It is concluded that alcohol abuse is associated with: (i) uncoupling of bone resorption and bone formation; (ii) reduced trabecular bone volume and thickness; and (iii) a mild mineralization defect.

Adult↗

Pathogenetic types of coxarthrosis and implications for treatment.

It is postulated that the variable clinical and radiological appearances of coxarthrosis are related to its pathogenesis and are important in deciding the choice of treatment. In a study of 150 patients the hip disorder was classified according to the presence or absence of some local anatomical defect which could predispose to mechanical overload, and also according to the presence or absence of some primary disorder which could cause cartilage degeneration. In addition, new bone formation and remodelling were assessed: this reparative response was most marked in joints with anatomical abnormalities ("hypertrophic OA") and least evident in those with previous inflammatory disease ("atrophic OA"). This study suggested that the behaviour of coxarthrosis is determined by three interacting factors: (1) cartilage degeneration, (2) excessive mechanical stress, and (3) the reparative bone response. The prognosis of the various types and the implications for treatment are discussed. Where anatomical abnormalities and mechanical features are dominant, cartilage loss is at first localised, remodelling is usually good and the hip can stabilise; in these cases osteotomy is often successful and prosthetic fixation is likely to remain secure. Where inflammatory and degenerative features predominate, reparative new bone formation is minimal and progression is more rapid; osteotomy is much less likely to be effective in these cases.

Hip Joint↗

Osteoarthritis of the hip: the patient behind the disease.

Previous epidemiological studies suggested that patients with osteoarthritis (OA) of the hip might constitute a definable subset of the population with characteristics that predispose them to joint failure. To investigate this possibility a comparative study of somatotype, bone density, disc degeneration, polyarticular joint degeneration, and soft-tissue calcification was carried out in 3 groups of individuals: (1) patients presenting with OA of the hip; (2) patients with acute femoral neck fracture; (3) healthy controls. OA of the hip was rare in patients with femoral neck fracture; conversely, patients with coxarthrosis did not have the low values for bone density seen in the fracture group. There were significant differences in somatotype in the 2 patient groups; 94% of those with OA were endomorphic mesomorphs. Polyarticular OA occurred with the same prevalence in the 2 groups of women, but among males there was a significantly greater involvement of knees and hands in the OA group than in the fracture group. The highest incidence of joint calcification was found in the fracture group and the lowest in the OA group. It was concluded that patients with OA of the hip form a definable subset of the general population. Within this group the appearances of hip OA are determined by 3 interacting factors: mechanical stress, cartilage degeneration, and bone response.

Aged↗