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Children and Bone Jennifer Brittain October 24, 2002 Osteoporosis $13.8 billion/year in healthcare costs (U.S.) – “pediatric disease with a geriatric outcome” – Key is PREVENTION – “Peak Bone Mass” (PBM) – Optimize bone mineral gains throughout childhood and adolescence Bone Physiology “Osteoblasts”—(OB’s) cells responsible for formation of bone tissue “Osteoclasts”—(OC’s) cells responsible for the breakdown of bone tissue Bone growth= activity of OB’s greater than that of OC’s Bone resorption= activity of OC’s greater than that of OB’s Bone Physiology – “Proper skeletal formation, growth and repair are critically dependent on the accurate orchestration of all the processes participating in the formation of endochondral bone at the growth plate.” – Bone Biology, Chapter 3 Basis of Bone Growth Bones grow in: – Width/diameter—involves formation externally and resorption internally – Length—enlargement of chondrocytes (cartilage cells) at the growth plate, followed by replacement with bone cells for mineralization Growth Plate The epiphyseal plate is the cartilaginous region separating bone into two distinct parts. The plate survives if the cartilage growth keeps pace with osteoblast invasion. When osteoblast activity increases beyond cartilage growth, the plate disappears and the “epiphyseal line” is seen. Bone Growth in Childhood Process begins approximately 6 weeks after fertilization and continues through adolescence. Some parts of the skeleton are developing through approximately 25 years of life. Growth Rate The most rapid skeletal growth is seen in infancy. A slow deceleration in the rate is seen around the age of 3 and on through puberty. Slight growth spurt appears around 8 years of age and distinctly decelerates immediately before puberty. Gains in Mass Most rapid gains in bone mass seen during adolescence ~25% of PBM acquired within the 2-year period at peak height velocity(rate). Maximal rates of bone mineral gains follow behind the peak height velocity (~612months) Bone Mineral Accrual of bone mineral continues after longitudinal growth has occurred. At peak growth velocity, 90% adult stature attained and only 57% of total bone mineral content (BMC) 90% of peak bone mass is gained by 18 yrs 5-12% bone mineral density gained during third decade Terminology Bone mineral content (BMC) is the measurement of amount of mineral in the bone (grams). Bone mineral density (BMD) is the measurement of mineral per area (grams per cm2) Bone mineral determinants 60-80% PBM is genetic – Likely that the effects are greater in mineral acquisition than in loss Racial differences (reduced risk of osteoporosis in blacks) – Some seen before puberty – Others emerge in late adolescence Determinants cont. Hormonal status (systemic): – Growth hormone (GH) Major influence before puberty Longitudinal bone growth impaired with deficiency Deficiency leads to reduced bone mineral/failure to acquire at expected rate Acts at growth plate by enhancing production of cartilage cells and then inducing IGF1 synthesis (a local regulator responsible for expansion of chondrocytes at growth plate) More bone mineral determinants Hormones cont. – Thyroid Deprived levels lead to deleterious effects on bone growth Direct effect on bone Indirect effect on GH and IGF-1 High levels increase growth rate and advance bone age Hormone Regulation cont. Estrogen – Direct effects on growth plate – Responsible for epiphyseal growth plate fusion (end of puberty) in females and males Glucocorticoids – Pharmacological doses cause stunted growth – Role in chondrocyte differentiation and hypertrophy Exercise and Bone Weight-bearing activity below a physiological threshold will lead to excessive resorption. Ex. Bone loss in spaceflight. Within physiological range, bone is maintained. Bone is gained as load/strain increases Exercise Cont. Greatest influence before and during puberty Bone mass increases due to early intense activity are carried into adulthood – Ex. BMD of former gymnasts, runners and dancers as high as 8-12% greater than agematched controls ( years later) Diet and Bone Protein: – Important role in bone development Influences peak bone mass – Protein malnutrition in developmental years can increase risk for osteoporosis and fracture later in life – Low intake impairs synthesis and action of IGF-1 (essential factor for longitudinal growth) – Significant association between ingested protein and bone mass gain in prepubertal children • Bonjour, JP et al. 2001 More Dietary Elements Calcium – Skeleton stores 95% of body’s calcium – In 2001, 90% of adolescent girls and 50% of boys consumed less than optimal Calcium amounts. Bachrach, 2001 – Contributes to bone mineral accrual during early adulthood and helps prevent loss at maturity Diet Cont. Vitamin D – Deficiency is a major cause of rickets in children and osteomalacia in adults Expansion of zone of growth plate coupled with impaired matrix calcification – Promotes mineralization – Suggestion that vitamin D receptors are found on OB and OC precursors Johnson, 1996 – Increases absorption of calcium (and phosphorous) Overview Peak bone mass is key to prevention of osteoporosis. Bones grow in length and mass due to a number of processes working together. Exercise can benefit bone health. Protein, calcium, and vitamin D are three important dietary components of bone health.