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Percentile distributions of bone measurements in Iowa children: the Iowa Bone Development Study.

Four hundred twenty-eight white children (200 boys and 228 girls) ages 4.5-6.5 yr had spine, hip, and whole-body bone mineral density (BMD) and bone mineral content (BMC) measured by dual-energy X-ray absorptiometry(DXA) as part of the Iowa Bone Development Study. Anthropometric measurements, including height, weight, and body mass index (BMI) were determined for each child at the time the bone measurements were made. The age- and gender-specific height percentile based on the 2000 CDC Growth Charts (www.cdc.gov/growthcharts/) was determined for each child. These percentiles were used to classify children into four groups as defined by the 25th, 50th,and 75th percentile cutpoints. Percentile distributions were determined within each height quartile group to delineate percentiles (5th, 25th, 50th, 75th, 95th) for BMD and BMC. Gender differences in BMD and BMC were investigated before and after stratification into height groups. Boys had higher age-height-weight-adjusted means for most BMD and BMC measures except spine BMD. Bone measurements increased with height quartile, indicating that taller children have greater BMD and BMC compared to shorter children of the same age and gender. Within any given quartile,mean BMD and BMC measurements were similar for boys and girls, with the exception of hip BMD, for which values were consistently higher for boys (p < 0.05). In addition, whole-body BMC values were higher for boys in quartiles 1 and 3 (p < 0.05). These bone measures provide norms for young white children and serve as a reference for comparison with other racial and ethnic groups, as well as with childhood populations that are at risk for osteopenia because of chronic disease. Gender, age, and height are useful clinical predictors of BMD and BMC in young children.

Bone Density↗

Amphiregulin is a novel growth factor involved in normal bone development and in the cellular response to parathyroid hormone stimulation.

Parathyroid hormone (PTH) is the major mediator of calcium homeostasis and bone remodeling and is now known to be an effective drug for osteoporosis treatment. Yet the mechanisms responsible for its functions in bone are largely unknown. Here we report that the expression of amphiregulin (AR), a member of the epidermal growth factor (EGF) family, is rapidly and highly up-regulated by PTH in several osteoblastic cell lines and bone tissues. Other osteotropic hormones (1alpha,25-dihydroxyvitamin D3 and prostaglandin E2) also strongly stimulate AR expression. We found all EGF-like ligands and their receptors are expressed in osteoblasts, but AR is the only member that is highly regulated by PTH. Functional studies demonstrated that although AR is a potent growth factor for preosteoblasts, it completely inhibits further differentiation. AR also strongly and quickly stimulated Akt and ERK phosphorylation and c-fos and c-jun expression in an EGF receptor-dependent manner. Moreover, AR null mice displayed significantly less tibial trabecular bone than wild-type mice. Taken together, we have identified a novel growth factor that is PTH-regulated and appears to have an important role in bone metabolism.

Amphiregulin↗

Osteoclast and its roles in calcium metabolism and bone development and remodeling.

Osteoclasts are multinucleated cells responsible for bone resorption and play important roles in normal skeletal development, in the maintenance of its integrity throughout life, and in calcium metabolism. During bone resorption, the cytoskeleton of osteoclasts undergoes extensive reorganization, with polarization and formation of ruffled borders to secrete acid and formation of sealing zone to prevent leakage. The differentiation and function of osteoclasts are in turn regulated by osteoblasts, stromal cells, and bone. They are also subjected to negative feedback regulation by extracellular and intracellular calcium concentrations.

Animals↗

Cortical bone development under the growth plate is regulated by mechanical load transfer.

Longitudinal growth of long bones takes place at the growth plates. The growth plate produces new bone trabeculae, which are later resorbed or merged into the cortical shell. This process implies transition of trabecular metaphyseal sections into diaphyseal sections. We hypothesize that the development of cortical bone is governed by mechanical stimuli. We also hypothesize that trabecular and cortical bone share the same regulatory mechanisms for adaptation to mechanical loads. To test these hypotheses, we monitored the development of the tibial cortex in growing pigs, using micro-computer tomography and histology. We then tested the concept that regulatory mechanisms for trabecular bone adaptation can also explain cortical bone development using our mechanical stimulation theory, which could explain trabecular bone (re)modelling. The main results showed that, from the growth plate towards the diaphysis, the pores of the trabecular structure were gradually filled in with bone, which resulted in increased density and cortical bone. The computer model largely predicted this morphological development. We conclude that merging of metaphyseal trabeculae into cortex is likely to be governed by mechanical stimuli. Furthermore, cortex development of growing long bones can be explained as a form of trabecular bone adaptation, without the need for different regulatory mechanisms for cortical and trabecular bone.

Adaptation, Physiological↗

Long-term effects of tissue expansion on cranial and skeletal bone development in neonatal miniature swine: clinical findings and histomorphometric correlates.

Progressive tissue expansion induces significant gross, histologic, and bony changes in skulls and long bones of neonatal miniature swine. These bony changes consist of erosion underlying tissue expanders, with bony lipping and bone deposition at the periphery of the expander. Cranial suture lines underneath expanders appear effaced and convoluted. Serial CT scans reveal decreased bone thickness and volume (p less than 0.02) but identical bone density (p = 0.60) beneath expanders. Increased bone volume and thickness occur at the periphery of expanders (p less than 0.02). Bone density (CT number) is unaffected by tissue expansion in both cranial and long bones. These findings have histomorphometric correlates: Osteoclastic bone resorption occurs underneath expanders with periosteal reaction at the periphery of expanders. Cranial sutures are similarly affected, but no cranial synostosis results. No changes to the inner table of the skull or stigmata of increased intracranial pressure were observed either in CT scans or in behavioral changes in long-term animals. The pathophysiology of bony changes is a remodeling effect, not one of simple pressure deformation. Increased bone resorption and complete inhibition of bone formation occur until the pressure is removed. Cranial bone is significantly more affected than long bone. After removal of the expanders, reparative bone remodeling begins within 5 days and nearly complete healing of the cranial defects occurs within 2 months (p less than 0.02). No plagiocephaly results despite early coronal suture changes. On the basis of this study, we conclude that tissue expansion causes significant but reversible effects, readily monitored by high-resolution CT scans, on neonatal and infant cranial and long bones.

Animals↗

Comparison of the effects of cassava (Manihot esculenta Crantz) organic cyanide and inorganic cyanide on muscle and bone development in a Nigerian breed of dog.

Effects of cassava (Manihot esculenta Crantz)-borne organic cyanide and inorganic cyanide in the form of sodium cyanide on bone and muscle development were investigated in eighteen dogs of Nigerian breed. After 16 weeks of stabilization in the laboratory from the time of purchase when the dogs were fed on the same diet, they were randomly assigned to three experimental groups of six dogs each. The control group was fed on rice while the other two groups were fed on either cassava (gari) or rice plus cyanide. The three diets were made isoenergetic and isonitrogenous by varying the quantity of meat incorporated into them. The results obtained after 14 weeks of feeding the respective diets indicated that there was retardation of muscle development in the gari-fed dogs. This may have resulted from gluconeogenesis from muscle protein associated with suppression of production of insulin by the pancreas in this group. The results indicated also that the effects of inorganic dietary cyanides on muscle development were different. Both forms of dietary cyanides, however, had no adverse effect on bone development.

Animals↗

Vascularization and endochondral bone development: changes in plasminogen activator activity.

Changes in plasminogen activator activity were studied during the sequential developmental stages of matrix-induced cartilage, bone, and bone marrow development. The morphological transitions were correlated with biochemical parameters. Morphologic evidence of vascularization of calcified hypertrophic cartilage was accompanied by a concomitant rise in plasminogen activator activity. Thereafter, a steady decline during mineralization and deposition of new bone was observed. Maximal plasminogen activator activity occurs at approximately the same time as peak activity of alkaline and acid phosphatase. These results imply a role for plasminogen activator during angiogenesis, vascular invasion, and attendant bone differentiation.

Animals↗

Calcium, phosphorus and human bone development.

Calcium intakes by girls and adult females should approximate or exceed the Recommended Dietary Allowances so that peak bone mass can be achieved during early adulthood and bone mass can be maintained thereafter until the menopause. Investigations of the relationship between dietary calcium consumption and measurements of bone mass or density strongly support the contention that adequate intakes of calcium by females contribute to greater values of bone mass through adolescence and into adulthood. Prospective studies have especially been robust in support of this relationship. Inadequate calcium intakes early in life may lead to low bone mass because of several possibilities. Three potential mechanisms for the development of low bone mass are proposed, and in all a role for elevated parathyroid hormone is emphasized. A likely mechanism contributing to low bone mass in the United States involves a low calcium:high phosphorus intake ratio, but this possibility has not been adequately tested with a prospective design. Future investigations are needed to address the etiologic risk factors influencing less than optimal development of bone mass in females living in affluent nations.

Adult↗