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Background: Osteoarthritis (OA) is one of the leading causes of disability in the world. Several genes are associated with the development of OA, and previous studies have shown adult children of individuals with OA have higher areal bone mineral density (BMD). Because childhood is an important period of growth and bone development, and body composition is known to be associated with BMD, we speculated that there may be differences in growth and bone measures among young children with a genetic predisposition to OA., Questions/purposes: (1) Do differences exist at baseline in anthropometric and peripheral quantitative CT (pQCT) measurements between children and grandchildren of individuals with OA and controls? (2) Do children and grandchildren of individuals with OA accrue bone longitudinally at a different rate than controls?, Methods: Longitudinal anthropometric (height, weight) and bone (cortical and trabecular volumetric BMD and cross-sectional area) measurements by pQCT were obtained at baseline and 18 and 36 months on children (n = 178) and grandchildren (n = 230) of 23 individuals with hip or knee arthroplasty resulting from OA and 23 sex-matched controls (16 females each). Grandchildren (age, 8-30 years) were further categorized as growing (premenarcheal or male < 14 years, n = 99) or mature (≥ 2 years postmenarchal or males ≥ 18 years, n = 96). The remaining 35 grandchildren could not be categorized and were excluded., Results: Mature granddaughters and grandsons of individuals with OA had greater trabecular volumetric BMD than controls (236 ± 24 and 222 ± 26 mg/cm, respectively, for granddaughters, difference of 14 [95% confidence interval {CI}, 1-28] mg/cm, p = 0.041 and 270 ± 22 and 248 ± 30 mg/cm, respectively, for grandsons, difference of 22 [95% CI, 1-42] mg/cm, p = 0.040). Greater trabecular volumetric BMD was observed in daughters of individuals with OA compared with daughters of controls (228 ± 28 and 212 ± 33 mg/cm, respectively, difference of 18 [95% CI, 3-30] mg/cm, respectively [p = 0.021]). Growing granddaughters and grandsons of controls had greater decreases in cortical volumetric BMD than grandchildren of individuals with OA (time-by-group [TG] based on mixed model [± standard error] -9.7 ± 4.3 versus -0.8 ± 4.4 mg/cm/year, respectively, for granddaughters, difference of 9.0 [95% CI, 2.4-15.5] mg/cm/year, p = 0.007 and -6.8 ± 3.3 versus 4.5 ± 3.4 mg/cm/year, respectively, for grandsons, difference of 11.3 [95% CI, 4.3-18.3] mg/cm/year, p = 0.002). Cortical volumetric BMD was maintained in sons of individuals with OA, but decreased in sons of controls (-0.0 ± 1.5 versus -4.3 ± 1.0 mg/cm/year, respectively, difference of 4.3 [95% CI, 0.7-7.8] mg/cm/year, p = 0.019 [TG]). There was a greater apparent decrease in cross-sectional area among daughters of individuals with OA than in controls (-4.6 ± 0.9 versus -1.7 ± 0.9 mm/year, respectively, difference of -2.9 [95% CI, -5.3 to -0.6] mm/year, p = 0.015 [TG])., Conclusions: Several anthropometric and bone differences exist between children and grandchildren of individuals with OA and controls. If these differences are confirmed in additional studies, it would be important to identify the mechanism so that preventive measures could be developed and implemented to slow or reduce OA development., Clinical Relevance: Differences in growth and bone development may lead to increased loads on cartilage that may predispose offspring to the development of OA. If these differences are confirmed in additional studies, it would be important to identify the mechanism so that preventive measures could be developed and implemented to slow or reduce OA development.

Background: Periods of growth are thought to be the best time to increase bone mineral content, bone area, and areal bone mineral density (aBMD) through increased loading owing to high rates of bone modeling and remodeling. However, questions remain regarding whether a benefit of exercise is seen at all bone sites, is dependent on pubertal status or sex of the child, or whether other factors such as diet modify the response to exercise., Questions/purposes: We asked: (1) Does bone-loading exercise in childhood consistently increase bone mineral content, bone area, or aBMD? (2) Do effects of exercise differ depending on pubertal status or sex? (3) Does calcium intake modify the bone response to exercise?, Methods: A literature search identified 22 unique trials for inclusion in this meta-analysis of the effect of exercise on bone changes by bone site, pubertal status, and sex. Sample sizes ranged from 16 to 410 subjects 3 to 18 years old with length of intervention ranging from 3 to 36 months. Fifteen of 22 trials were randomized (child randomized in nine, classroom/school randomized in six) and seven were observational trials. Ten trials were Level 2 and 11 were Level 3 based on the Oxford Centre for Evidence-Based Medicine criteria. Random effects models tested the difference (intervention mean effect-control mean effect) in percent change in bone mineral content, bone area, and aBMD. Meta-regression was used to identify sources of heterogeneity and funnel plots were used to assess publication bias., Results: Children assigned to exercise had greater mean percent changes in bone mineral content and aBMD than children assigned to the control groups. Mean differences (95% CI) in bone mineral content percent change between intervention and control groups at total body (0.8; 95% CI, 0.3-1.3; p = 0.003), femoral neck (1.5; 95% CI, 0.5-2.5; p = 0.003), and spine (1.7; 95% CI, 0.4-3.1; p = 0.01) were significant with no differences in bone area (all p > 0.05). There were greater percent changes in aBMD in intervention than control groups at the femoral neck (0.6; 95% CI, 0.2-1.1; p = 0.006) and spine (1.2; 95% CI, 0.6-1.8; p < 0.001). Benefit of exercise was limited to children who were prepubertal (bone mineral content: total body [0.9; 95% CI, 0.2-1.7; p = 0.01], femoral neck [1.8; 95% CI, 0.0-3.5; p = 0.047], spine [3.7; 95% CI, 0.8-6.6; p = 0.01], and aBMD: femoral neck [0.6; 95% CI, -0.1-1.2; p = 0.07], spine [1.5; 95% CI, 0.7-2.3; p < 0.001]), with no differences among children who were pubertal (all p > 0.05). Changes in aBMD did not differ by sex (all p > 0.05), although the number of studies providing male-specific results was small (six of 22 eligible studies included boys). There was significant heterogeneity in bone mineral content and bone area for which a source could not be identified. Heterogeneity in spine aBMD was reduced by including calcium intake and intervention length as covariates. Three trials designed to determine whether calcium intake modified the bone response to exercise all reported a greater effect of exercise on leg bone mineral content in children randomized to receive supplemental calcium than those receiving placebo., Conclusions: Exercise interventions during childhood led to 0.6% to 1.7% greater annual increase in bone accrual, with effects predominantly among children who were prepubertal. If this effect were to persist into adulthood, it would have substantial implications for osteoporosis prevention. It is important to identify sources of heterogeneity among studies to determine factors that might influence the bone response to increased exercise during growth., Level of Evidence: Level II, therapeutic study.

Objectives: The purpose of this study was to determine the effect of sports participation on cortical bone in the tibia., Methods: 53 female collegiate athletes (25 cross-country, 16 soccer, and 12 volleyball) and 20 inactive controls had the left distal 20% tibia scanned by pQCT. Cortical volumetric BMD (vBMD) was measured within the cortical shell at the anterior, posterior, medial, and lateral regions and standard deviations were calculated., Results: Total vBMD was greater in the control group (1161±5 mg/mm(3)) than each of the sports (p<0.05). Soccer players (1147±5 mg/mm(3)) had greater vBMD than volleyball players (1136±7 mg/mm(3)) (p<0.05), but similar to cross-country runners (1145±5 mg/mm(3)). Cortical thickness was greatest in soccer players (4.1±0.1 mm), while cross-country and control subjects (3.8±0.1 mm) had greater thickness than volleyball players (3.4±0.1 mm)(p<0.05). Periosteal circumference was greater in volleyball players (71±1.4 mm) than soccer, cross-country, and control subjects (68±0.9, 69±0.8, and 66±1 mm, respectively; all, p<0.05). vBMD variation within the cortical shell was greater among control subjects (70±6 mg/cm(3)) than each of the athlete groups, with soccer players having lower variation than cross country runners (within-in person SD 36±6 mg/cm(3) and 54±5 mg/cm(3) respectively; p<0.05)., Conclusion: These results indicate bone geometry and distribution within the cortical shell of the tibia varies depending upon sporting activities of young women.

Objective: To determine whether an active rural lifestyle during childhood and adolescence, defined as low farm mechanization, was associated with bone measures later in life., Methods: DXA bone data from total body, hip and spine, and pQCT data from 4% and 20% distal radius were obtained on 330 individuals (157 women) aged 20-66 years who farmed at least 75% of their lives. Primary bone outcomes included areal bone mineral density (aBMD), aBMD Z-scores, cortical and trabecular volumetric BMD, cortical thickness and periosteal circumference. Relationship between bone and recall of level of farm mechanization as a child was determined after stratifying by sex and controlling for covariates., Results: Controlling for covariates, females from low mechanized farms had higher femoral neck (FN) bone area (p=0.03) than those on high or moderate mechanized farms. No group differences in pQCT ulna measurements or z-scores were found in either gender., Conclusion: A low farm mechanization level (high physical activity) prior to 20 years of age is associated with greater FN bone area in females. Future research that includes type and amount of physical activity performed will contribute to growing knowledge of how and when regular physical activity during childhood and adolescence affects adult bone health.

The age women reach menarche may affect bone length and mass. Some studies show an earlier menarcheal age (MA) results in a shorter stature and increased body fat. We hypothesized that Hutterite women have a shorter height and limb length, but greater bone mass and areal bone mineral density (aBMD) than non-Hutterites. Results are from a secondary analysis of 344 (198 Hutterite) healthy, pre-menopausal women aged 20-40 years who participated in the South Dakota Rural Bone Health Study. Bone measures were obtained by DXA (spine, hip and total body) and pQCT (4 and 20% distal radius). MA correlated with year of birth (r = -0.10, P = 0.08) indicating a trend toward a younger MA for women born in more recent years. MA was inversely associated with current weight (r = -0.11, P < 0.05), percent body fat (r = -0.16, P < 0.01), femoral neck BMC (r = -0.18, P = 0.003), femoral neck aBMD (r = -0.21, P < 0.001), hip aBMD (r = -0.22, P < 0.001) and trabecular volumetric BMD (vBMD) (r = -0.14, P = 0.03). Hutterite women had a younger MA than non-Hutterite women (12.3 +/- 1.3 vs. 13.0 +/- 1.3 yr, P < 0.001). In final regression models controlling for diet and activity patterns, Hutterite compared to non-Hutterite women had shorter standing height (162 +/- 0.4 vs. 166 +/- 0.4 cm, P < 0.001), forearm length (258 +/- 0.8 vs. 261 +/- 0.9 mm, P = 0.04); and leg length (76 +/- 0.2 vs. 77 +/- 0.3 cm, P < 0.01) as hypothesized, but MA did not predict these outcomes. In conclusion, younger MA in Hutterite women did not explain their shorter standing height and limb lengths, but total hip aBMD was inversely associated with MA and greater in Hutterite than non-Hutterite women.

Objective: To elucidate the relationship between bone geometry and onset of walking in former term and preterm children., Study Design: We conducted a cross-sectional study of 128 preschool children aged 3 to 5 years who underwent peripheral quantitative computerized tomography measures of bone size at the distal tibia. Linear models were developed, stratifying by sex, to determine whether bone differences between children born term and preterm were caused by differences in walking age., Results: Children with a history of preterm birth walked later than children born at term (12.4 +/- 0.5 versus 10.9 +/- 0.2 months; P = .004); however, gestation-corrected walking age (11.4 +/- 0.5 for children born preterm) did not differ. In multiple regression analysis, boys born preterm had larger periosteal and endosteal circumferences and smaller cortical thickness and area than boys born term (least square means, 49.7 +/- 1.3 mm, 43.0 +/- 1.8 mm, 1.1 +/- 0.11 mm, and 49.3 +/- 3.2 mm2 versus 47.0 +/- 0.5 mm, 38.5 +/- 0.7 mm, 1.4 +/- 0.04 mm, and 56.9 +/- 1.2 mm2, respectively; all P < .05). Preterm birth remained statistically significant after adding the age of walking to the models, but no longer significant when current activity levels were included., Conclusion: Greater periosteal and endosteal circumferences, with smaller cortical bone thickness and area, were found in former preterm boys, but not girls, and were explained by differences in current activity levels, not age of walking.

Exercise and nutrition are independently recognized as important modifiable lifestyle factors essential for optimal bone health during growth. In this review, we discuss the effect of dietary calcium, vitamin D and protein alone and in combination with exercise on bone mass and strength in children and adolescents. Recent intervention studies in children now provide evidence that exercise and calcium may interact with each other to enhance bone health, but the mechanism underlying this effect is not well understood. Vitamin D is also important for bone health through its action on calcium absorption, and both dietary protein and total energy intake can also alter bone metabolism through their influence on growth factors such as insulin-like growth factor I. However, whether these factors act synergistically with exercise to enhance bone accrual has not been examined. Therefore, while exercise and nutrition are both independently important for skeletal development, there remain many unanswered questions as to whether combinations of these factors interact to enhance skeletal health during growth. Current evidence suggests that regular weight-bearing exercise and adequate dietary calcium intakes (around 1,000 mg per day) may be required to optimize bone health; however, exercise would appear to be more important for optimizing bone strength because it has a direct effect (e.g. via loading) on bone mass and structural properties, whereas nutritional factors appear to have an indirect effect (e.g. via hormonal factors) on bone mass.

During rapid growth, increased body weight and muscle strength result in increased loads on bone. Bone adapts to these increased strains by increasing bone modeling and remodeling. As the growth rate decreases, bone that was formed as a result of these adaptations continues to mineralize and "catch up", and bone modeling and remodeling decreases. Bone benefits of exercise in childhood are reported in some studies, although we observed less BMC gain at trabecular-rich sites during the peri-pubertal period in children who jumped than those who did not. Data from 13 existing pediatric exercise studies were compiled to determine whether similar patterns of age-related bone changes could be identified, and whether the bone benefit of exercise differed depending upon pubertal stage. The benefit of exercise on total body BMC gains occurred across all ages, whereas greater exercise-induced gains at the spine and hip were observed in younger children compared to older children. The majority of studies found a positive effect of exercise on bone, but typically this involved limiting the analysis to specific sub-populations (i.e., higher calcium intake, lower baseline activity levels, smaller body size). Limitations of the studies published to date are discussed.

During the last decade a greater appreciation has developed for determining factors that influence bone accretion in healthy children. Nutritional factors that may contribute to bone accretion in infants and toddlers include maternal nutritional status during pregnancy, type of infant feeding, calcium and phosphorus content of infant formula, introduction of weaning foods, and diet during the toddler and preschool years. Maternal vitamin D deficiency during pregnancy is associated with disturbances in neonatal calcium homeostasis, and maternal calcium deficiency leads to reduced neonatal bone mineral content (BMC). Preterm infants are at increased risk of osteopenia, and, although the use of high mineral formula has reduced the risk of osteopenia in these infants, it has not eliminated it. The reason for the long-term bone deficiency among preterm infants is not clear, although lower physical activity levels have been suggested as a potential cause. Studies find that human milk-fed infants have lower bone accretion than do formula-fed infants; that the greater the mineral content of formula, the greater the bone accretion; and that the inclusion of palm olein oil in infant formula may reduce bone mineral accretion. Bone accretion is not influenced by the timing of the introduction of weaning foods, despite higher serum parathyroid hormone (PTH) concentrations among infants who receive solids earlier. There is evidence of calcium intake-by-gene and calcium intake-by-physical activity interactions among toddlers and young children. The long-term effects of these early nutritional influences on later bone health are unknown.

Serum carboxy-terminal propeptide of human type I collagen (PICP) concentrations, as a marker for bone formation, and urinary pyridinium (Pyd) cross-link concentrations, as a marker of bone resorption, were determined in 66 healthy infants aged 1-18 months who are being studied longitudinally. We hypothesized that there would be a positive correlation of growth velocity, increase in bone area, and bone mass accretion rates with PICP and Pyd cross-link concentrations. Since osteocalcin is currently used as a marker of bone formation, serum osteocalcin concentrations were also measured. Mean serum PICP and urinary Pyd cross-link concentrations were significantly greater than adult concentrations. Future growth velocity, increase in bone area, and bone mass accretion rates were not associated with PICP, Pyd cross-link, or osteocalcin concentrations. Growth velocity during the 3 months preceding sample collection correlated with serum PICP, Pyd/kg, and osteocalcin concentrations (r = 0.474, p < 0.001; r = 0.379, p < 0.001; and r = 0.516, p < 0.001, respectively). Previous increase in bone area correlated with serum PICP concentrations (r = 0.359, p = 0.01). The relationship between the infant's previous bone mass accretion rate and PICP was of borderline significance (r = 0.281, p = 0.055). In summary, normative data for PICP, Pyd cross-link concentrations, and parameters of bone growth are provided for infants 1-18 months of age and indicate that these markers reflect past and current bone metabolism and may be helpful in monitoring bone disorders in infants.