Longitudinal Growth and pQCT Measures in Hutterite Children and Grandchildren Are Associated With Prevalence of Hip or Knee Replacement Resulting From Osteoarthritis in Parents and Grandparents
Authors: Weidauer Lee , Beare Tianna , Binkley Teresa , Minett Maggie , Specker Bonny 
Published: June 2018

Abstract

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/cm3, respectively, for granddaughters, difference of 14 [95% confidence interval {CI}, 1-28] mg/cm3, p = 0.041 and 270 ± 22 and 248 ± 30 mg/cm3, respectively, for grandsons, difference of 22 [95% CI, 1-42] mg/cm3, 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/cm3, respectively, difference of 18 [95% CI, 3-30] mg/cm3, 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 [T*G] based on mixed model [± standard error] -9.7 ± 4.3 versus -0.8 ± 4.4 mg/cm3/year, respectively, for granddaughters, difference of 9.0 [95% CI, 2.4-15.5] mg/cm3/year, p = 0.007 and -6.8 ± 3.3 versus 4.5 ± 3.4 mg/cm3/year, respectively, for grandsons, difference of 11.3 [95% CI, 4.3-18.3] mg/cm3/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/cm3/year, respectively, difference of 4.3 [95% CI, 0.7-7.8] mg/cm3/year, p = 0.019 [T*G]). 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 mm2/year, respectively, difference of -2.9 [95% CI, -5.3 to -0.6] mm2/year, p = 0.015 [T*G]).

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.