Endochondral bone growth, bone calcium accretion, and bone mineral density: How are they related?

Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok, Thailand.
The Journal of Physiological Sciences (Impact Factor: 1.9). 05/2012; 62(4):299-307. DOI: 10.1007/s12576-012-0212-0
Source: PubMed


Endochondral bone growth in young growing mammals or adult mammals with persistent growth plates progresses from proliferation, maturation and hypertrophy of growth plate chondrocytes to mineralization of cartilaginous matrix to form an osseous tissue. This complex process is tightly regulated by a number of factors with different impacts, such as genetics, endocrine/paracrine factors [e.g., PTHrP, 1,25(OH)(2)D(3), IGF-1, FGFs, and prolactin], and nutritional status (e.g., dietary calcium and vitamin D). Despite a strong link between growth plate function and elongation of the long bone, little is known whether endochondral bone growth indeed determines bone calcium accretion, bone mineral density (BMD), and/or peak bone mass. Since the process ends with cartilaginous matrix calcification, an increase in endochondral bone growth typically leads to more calcium accretion in the primary spongiosa and thus higher BMD. However, in lactating rats with enhanced trabecular bone resorption, bone elongation is inversely correlated with BMD. Although BMD can be increased by factors that enhance endochondral bone growth, the endochondral bone growth itself is unlikely to be an important determinant of peak bone mass since it is strongly determined by genetics. Therefore, endochondral bone growth and bone elongation are associated with calcium accretion only in a particular subregion of the long bone, but do not necessarily predict BMD and peak bone mass.

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    • "There is a higher incidence of clinical fractures in obese postmenopausal women [16] and in overweight adolescents [17–19]. Several animal studies supported this negative effect on bone strength [20, 21], bone mineral density [22], and bone formation [15]. However, the traditional view of obesity is that overweight is beneficial to bone [11, 23–25] since the femoral neck of obese women especially with osteoporotic bones showed a reduction in fracture risk [25] and an increase in BMD [23]. "
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    Full-text · Article · Feb 2014 · International Journal of Endocrinology
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    • "In mammals, the endochondral bone growth starts during early gestation, accelerates at midgestation and continues until sexual maturity (Wongdee et al. 2012). The bone growth "
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    ABSTRACT: We studied the effect of metal mixture (MM), comprising of As, Cd and Pb, in developing female rat skeleton from gestation day-5 until postnatal day-60 (P-60). MM resulted in synergistic inhibition in viability and differentiation of osteoblasts in vitro, likely induced by reactive oxygen species. MM, administered at their most frequently occurring concentrations present in the ground-water of India, i.e. As: 0.38ppm, Pb: 0.22 ppm and Cd: 0.098 ppm or 10× of the ratio to developing rats exhibited a synergistic decrease in ex vivo mineralization of bone marrow stromal (osteoprogenitor) cells. MM group showed a dose-dependent attenuation in weight and axial lengths, and shortening of tibias at P-60. Furthermore, the growth plate was shortened, which was associated with shorter proliferative- and hypertrophic zones, decreased parathyroid hormone-related protein and Indian hedgehog expression in the chondrocytes, reduced primary- and secondary spongiosa, and hypomineralized osteoids - a major characteristic of osteomalacia. In addition, compared to the control, MM treated rats were clearly osteopenic based on BMD, micro-architecture, biomechanical strength, and particularly the biochemical profile, that suggested high turnover bone loss. Finally, in comparison to the control, the fracture healing ability of MM group was delayed and accompanied by inferior quality of the healed bone. Together, these data demonstrated that the mixture of As, Cd and Pb induced synergistic toxicity to developing skeleton thereby diminishing modeling-directed bone accrual, inducing osteopenia and dampening fracture healing.
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    No preview · Article · Jun 2013 · Molecular and Cellular Biochemistry
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