Christine M. Schnitzler

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.

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 postmenopausal 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.

Bone quality: A determinant for certain risk factors for bone fragility

SummaryLow 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. American and African blacks have lower fragility fracture rates than whites for different reasons: American blacks because of higher BMD, and African blacks because of higher bone turnover, better hip BMD, and sturdier trabeculae.

Histomorphometry of Iliac Crest Trabecular Bone in Adult Male Baboons in Captivity

SummaryDat 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.

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.

Pathogenetic types of coxarthrosis and implications for treatment

SummaryIt 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.ZusammenfassungDie unterschiedlichen klinischen und radiologischen Erscheinungsformen einer Coxarthrose stehen in enger Beziehung zu ihrer Pathogenese und sind für die Wahl der Behandlung von großer Bedeutung.In einer Studie an 150 Patienten erfolgte eine Einteilung gemäß vorhandener anatomischer Defekte, die zu einer mechanischen Fehlbelastung führen und gemäß vorhandener Grunderkrankungen, die zu einer Degeneration des Gelenkknorpels führen.Zusätzlich werden Knochenneu- und Knochenumbildung beurteilt. Diese reparativen Reaktionen sind in Gelenken mit anatomischen Abnormitäten besonders ausgeprägt („hypertrophe Osteoarthrose”), hingegen in Gelenken mit vorausgegangenen entzündlichen Erkrankungen weniger vorhanden („atrophe Osteoarthrose”).Die Studie sagtweiterhin aus, daß der Verlauf einer Coxarthrose von drei wesentlichen Faktoren bestimmt ist, die sich gegenseitig beeinflussen.1.Degeneration des Gelenkknorpels2.Massive mechanische Überlastung3.Reparative Vorgänge. Verlauf and Prognose der unterschiedlichen Typen sowie Folgerungen für ihre Behandlung werden diskutiert. Stehen anatomische Abnormitäten und mechanische Merkmale im Vordergrund, zeigt sich als erstes ein Verschleiß des Gelenkknorpels. Die Knochenneubildung ist gewohnlich gut, das Gelenk stabilisiert sich. In diesen Fällen sind Osteotomien häufig erfolgreich und eine Prothesenversorgung dauerhaft. Überwiegen entzündliche und degenerative Merkmale, ist die Knochenneubildung gering, der pathologische Verlauf ist gewöhnlich sehr schnell. Osteotomien sind in diesen Fällen wenig erfolgversprechend.

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.

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 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.

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.