Developmental Origins of Osteoporotic Fracture: the Role of Maternal Vitamin D Insufficiency

Abstract

Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most efforts in fracture prevention have been directed at retarding the rate of age-related bone loss and reducing the frequency and the severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterized in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone-mineral content, but not volumetric bone density, than girls. Furthermore, there is a disassociation between the peak velocities for height gain and bone mineral accrual in both genders. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors (e.g., cigarette smoking). In addition to these modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birthweight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of endocrine systems such as the GH/IGF-1 and parathyroid hormone/vitamin D axes. Maternal vitamin D insufficiency is associated with reduced bone mineral acquisition during intrauterine and early postnatal life. Furthermore, both low birth size and poor childhood growth are directly linked to the later risk of hip fracture. The optimization of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.

Resurrection of vitamin D deficiency and rickets

“…In utero, vitamin D deficiency results in reduced intrauterine long bone growth and slightly shorter gestation (121). This has been linked to increased risk of osteoporosis and fractures later in life (24,60,61,82,122). Children born and raised at latitudes below 35° for the first 10 years have a 50% reduced risk of developing multiple sclerosis later in life (103,104).…”

“…Because of the practice of purdah or wearing a burka (45,46), avoidance of exposure of any skin to sunlight, and the fact that few foods are fortified with vitamin D, upward of 35-80% of children in Saudi Arabia (46,47), India (48), Turkey (29), New Zealand (49), Israel (50), Egypt (51), Hong Kong (52), China (53), Libya (54), Lebanon (55), Spain (56), Australia (57), San Diego, California (58), and the southeastern United States (59) are vitamin D deficient. When the deficiency occurs during fetal life, there is data to suggest that this may cause an increased risk of hip fractures and bone loss later in life (56,60,61). Subclinical vitamin D deficiency in neonates is associated with a normal serum calcium level, low 25(OH)D concentration (typically between 10 and 20 ng/ml), and elevated serum PTH, 1,25(OH) 2 D and alkaline phosphatase levels (30)(31)(32).…”

Vitamin D, not iron, is the main nutrient deficiency in pre-school and school-aged children in Mexico City: a cross-sectional study

“…There is a concern, not only about new cases of rickets and metabolic disease of the bone in the newborn or the possible alterations on other systems, but also about the degree of skeletal mineralization that may predispose one to fractures in childhood and to later development of early osteoporosis with its associated costs and risks (26). Vitamin D deficiency and its impact on bone health have already been described in pregnant mothers, newborns, and preschool children in all five continents (27).…”

Experience of famine and bone health in post-menopausal women

“…Maternal lifestyle, such as smoking, diet (in particular the vitamin D deficiency) and physical activity appears to modulate the bone mineral acquisition during intrauterine life, and low birth size is also positively associated with hip fracture in later life. 26,27 It is possible that vitamin D insufficiency in the mother or during childhood contributes to the observed associations 28 and that the observed association between bone density and cardiovascular disease stems from a development origin and both disorders. Unfortunately, this information was not available.…”