Bone Mass from Childhood to Adulthood

Sammanfattning: Attaining high peak bone mass (PBM), the highest bone mass value in life which is reached in young adulthood, is important as it reduces the risk of having low bone mass in old age69, 80. Low bone mass is associated with high fracture risk3, 60. Osteoporosis is the result of bone loss, a physiological process related to aging and/or low PBM. It would therefore be of great value to identify children at risk of reaching low PBM for possible interventions. But the level of correlation, in the thesis referred to as “tracking”, in bone mass from childhood to adulthood is unclear. Making predictions about adult bone mineral density (BMD) from childhood measurements is difficult as bone properties change rapidly during growth59. Most studies that have evaluated the question are either cross-sectional, have a short follow-up time or end close to the final growth spurt, making reliable predictions difficult. There are some reports suggesting that a childhood excess62, 76 or deficit77, 116 in BMD remains in adulthood, and the few prospective studies that have addressed the question infer that there is a partial “tracking” in BMD during growth. Longitudinal studies with serial measurements that cover both the pre- and post-pubertal phases and that follow the participants until peak bone mass (PBM) would provide data with a higher level of evidence and thereby increase our knowledge. In this thesis, with a long-term prospective study design, we have evaluated the “tracking” of bone mass from childhood to adulthood, and specifically evaluated two risk factors linked to low BMD. The first is a fracture in childhood which has been an event identified as associated with low BMD both in childhood31 and in adulthood54. The second is premature birth in relation to low birth weight, since both traits have been associated with low PBM67, 84. We invited subjects from three previous studies63, 86-87 published during 1981–1985 to be re-measured almost three decades after the initial measurement. The study subjects with a mean age of 10 years (range 3–17) at the first measurement were re-measured a mean 27 (range 25–29) years later. Bone traits were prospectively evaluated with singlephoton absorptiometry (SPA) in 214 individuals consisting of three cohorts: healthy control subjects, children with fracture during childhood and children born preterm, either small for gestational age (SGA) or appropriate for gestational (AGA). In the second cohort we evaluated bone traits prospectively by dual-energy X-ray absorptiometry (DXA) in 121 children from the Pediatric Osteoporosis Prevention (POP) study, an exercise intervention study that is primarily designed to assess 10 musculoskeletal development and fracture risk in response to increased physical education in school children. The study subjects with a mean age of 8 years (range 7– 9) at the first measurement were re-measured a mean 11 (range 10–12) years later. Our aim was to evaluate (i) whether a bone mass scan in childhood can be used to predict bone mass in adulthood, (ii) whether children who sustain a fracture are at increased risk of reaching low adult BMD and (iii) whether prematurely born children, either AGA or SGA, are at increased risk of reaching low adult BMD. The correlation coefficients (r) between pre-pubertal and young adulthood measurements for distal radius BMC and BMD varied between 0.35 and 0.64 and for femoral neck BMC, BMD and bone area it varied between 0.37 and 0.65. A childhood fracture in men was associated with a low BMC Z-score (–0.4 (95% CI –0.6, –0.1)) and low BMD Z-score (–0.4 (95% CI –0.7, –0.1)) at baseline and with a low BMC Zscore (–0.5 (95% CI –0.8, –0.2)) and low BMD Z-score (–0.4 (95% CI –0.7, –0.1)) at follow-up. Preterm-born children were still shorter in adulthood (p=0.03), they also had lower femoral neck (FN) BMC, FN BMD, tibial cortical BMD, tibial crosssectional area and SSI than controls (all p-values 0.001 to <0.05). The deficits were driven by lower bone traits in preterm SGA individuals, while no differences were seen in preterm AGA individuals compared to controls. This thesis shows that an individual pediatric bone mass scan, regardless of whether it is evaluated with SPA or DXA and independent of the measured skeletal region, has poor ability to predict an adult bone mass value. We also show that a childhood fracture in men was associated with low BMD and smaller bone size in young adulthood and that prematurity and being born SGA is another risk factor for low bone mass in young adulthood.