derived from pluripotential stromal precursor cells (sometimes called mesenchymal stem cells) and are the active cells that lay down new bone during skeletal growth and remodeling. Mesenchymal stem cells are very similar too and likely arise from the pericytes or perivascular cells present just deep to the endothelium of blood vessels. A very active area of basic science and translational research is harnessing the regenerative potential of mesenchymal stem cells to treat a variety of diseases (4, 5 and 6). As the bone matures, osteoblasts become encased in the new bone. They produce alkaline phosphatase, an enzyme that is often used to identify osteoblasts and osteoblastic activity. Once they become encased in osteoid, they become relatively quiescent and are termed osteocytes. In mature bone, osteocytes are located extremely far away from neighboring cells, and communicate with other cells through long cytoplasmic processes. The osteocytes remain quiescent until stimulated by hormonal or mechanical factors to begin to reabsorb or lay down bone. Although osteoblasts and osteocytes are thought of as cells responsible for building new bone, they also are able to rapidly reabsorb small quantities of bone. They are able to do this in a relatively rapid manner, in contrast to osteoclasts, which require cellular differentiation and recruitment to reabsorb bone. Thus, they are the first cells that the body activates when bone reabsorption is required (7).
vitamin D deficiency as well as directly deregulating normal calcium excretion. Because of the crucial role of vitamin D in calcium metabolism, the National Academy of Sciences and the American Academy of Pediatrics recommend 200 IU per day of vitamin D (41). This dose will prevent physical signs of vitamin D deficiency and maintain serum 25-hydroxyvitamin D at or above 27.5 nmol/L (11 ng/mL). Many professional bodies and experts are currently advocating for increased intake of vitamin D for healthy children, with credible recommendations ranging from 400 to 1000 IU (42, 43). The generic name of 1,25-dihydroxyvitamin D is calcitriol. Recent studies found that vitamin D also has a variety of extraskeletal effects, including modulating the immune response, and as a chemoprotective agent against certain cancers (42, 43 and 44).
with decreased bone mass, and there is an association between delayed puberty and low bone mass in boys, suggesting a positive role for androgens regulating bone mass (54).
TABLE 6-1 Dietary Calcium Requirements
of a deformity in a growing child with an endocrine disorder until the endocrinopathy is also treated.
is caused by renal tubular phosphate wasting in isolation (79). Renal tubular abnormalities including Fanconi syndrome feature renal wasting of phosphate, calcium, magnesium, and bicarbonate. Alkaline phosphatase is deficient only in one rare recessive condition, appropriately called hypophosphatasia.
day for all healthy children and adults (43). Sunlight exposure also prevents rickets. Two hours per week of summer sunshine at the latitude of Cincinnati (39 degrees North) is sufficient to produce adequate vitamin D in the skin. However, during the winter months in Edmonton (52 degrees North), there is insufficient UVB exposure to allow for adequate intrinsic production of vitamin D (68). A recent national survey in Canada estimated a prevalence of vitamin D deficiency rickets of at least 3 per 100,000 children, with a higher risk among breastfed children and those dwelling in the north (88).
TABLE 6-2 Classification of Rickets According to What Is Lacking at the Osteoblast-Bone Interface
remain autonomous and maintain a hyperparathyroid state even if the end stage renal disease is treated by transplantation. In this case, the ongoing hyperparathyroidism is described as tertiary rather than secondary.
Dietary phosphate restriction
Phosphate binding agents, especially those that contain calcium
Vitamin D particularly calcitriol to decrease the secondary hyperparathyroidism as well as to treat clinical rickets or osteomalacia
Restoration of renal function by transplantation often improves the musculoskeletal manifestations.
affected are old, and not likely seeing paediatric orthopaedists. However, the NIH emphasizes that “sub-optimal bone growth in childhood and adolescence is as important as bone loss to the development of osteoporosis.” An epidemiologic study compared rickets mortality in 1942 to 1948 with hip fracture rates in 1986 to 1993 across birth regions in the United States, and found a very high correlation, suggesting that early deficiency of vitamin D could have important effects on the skeleton decades later (136). The recommended intake of calcium for children aged 9 to 17 is 1300 mg per day, and it is estimated that only 10% of girls and 25% of boys meet this minimum requirement (135). While consumption of dairy-based beverages supplying calcium has declined, consumption of carbonated beverages has increased (137). Phosphoric acid is used in cola soft drinks, and teenage girls who drink soft drinks are three to four times more likely to report fractures than those who do not, the association being strongest among active girls drinking cola (138). A meta-analysis of calcium supplementation including 19 randomized trials and 2859 children showed no effect of calcium supplementation alone on BMD at the femoral neck or the lumbar spine (139). Self-reported physical activity in adolescence (but not during adulthood), on the other hand, was a strong determinant of BMD after menopause (140). A meta-analysis of 22 randomized controlled trials of physical activity in childhood showed 1% to 5% increases in bone mineral accrual among the exercising groups, with a greater effect before puberty was complete (141). Vitamin D supplementation has not been so well studied but is receiving increasing attention, with advocates pointing to epidemiologic studies linking vitamin D intake or latitude to lower incidences of cancer and cardiovascular disease as well as to improved bone health (43). A challenge is determining the appropriate level for supplementation of vitamin D, although recent opinion suggests increasing the amount of oral vitamin D3 to 1000 units per day for both children and adults (43).