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May 12, 2022
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Sex steroid levels, bone markers align with skeletal development in boys during puberty

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Serum levels of sex steroids and bone metabolism markers align with skeletal development in boys during puberty, though development can vary based on pubertal stage, according to study findings published in Bone.

“Serum levels of sex steroids, insulin-like growth factor I and bone metabolism markers reflect skeletal development during puberty,” Bruno Lapauw, MD, PhD, professor in the department of endocrinology at Ghent University in Belgium and unit for osteoporosis and metabolic bone diseases at Ghent University Hospital, and colleagues wrote. “However, skeletal development during puberty is nonlinear, and we found that the relations between skeletal indices and hormonal parameters are nonlinear as well, and dependent on the respective maturation stage and skeletal site.”

Bruno Lapauw, MD, PhD
Lapauw is a professor in the department of endocrinology at Ghent University in Belgium and unit for osteoporosis and metabolic bone diseases at Ghent University Hospital.

Researchers analyzed data from 118 healthy boys aged 5 to 17 years with repeated bone and biochemical measurements performed at baseline and a 2-year follow-up (mean age, 12.4 years). The Tanner staging method was used to determine pubertal status, with stage 1 defined as pre-puberty, stages 2 and 3 as early puberty and stages 4 and 5 as late puberty. Peripheral quantitative CT was used to calculate trabecular bone density and area; cortical bone density, area and thickness; and periosteal and endosteal circumference. Sex hormone levels were measure through venous blood samples.

Bone mineral density increases during puberty

Whole body bone mineral content and areal bone mineral density increased in the study cohort with each Tanner stage (P < .001). Lumbar spine BMD increased significantly only from stage 3 to stage 5 (P < .043), cortical bone area increased between all stages except between 2 and 3 (P < .003), and cortical volumetric BMD increased between stages 1 and 2 and stages 4 and 5 (P < .004 for both). Periosteal circumference and endosteal circumference increased between stages 2 and 3 (P < .013 for both). Cortical thickness increased between all stages except between 2 and 3 (P < .05).

“Procollagen type 1 N-terminal propeptide (P1NP) and carboxy-terminal collagen crosslinks (CTX) were positively associated with periosteal circumference in early puberty and endosteal circumference in late puberty (P < .05 for both). Both markers were negatively associated with whole body and lumbar spine bone mineral content and areal BMD and cortical density, area and thickness in late puberty (P < .002 for all). P1NP was positively associated with trabecular area in early puberty and negatively associated in late puberty (P = .002). CTX was negatively associated with cortical density in early puberty (P = .009) and trabecular density in late puberty (P = .02).

Testosterone increases with skeletal development

Total testosterone and calculated free testosterone levels were positively associated with height at all stages (P < .001 for all), whole-body areal BMD during prepuberty (P < .02 for all), whole-body bone mineral content, trabecular area, periosteal circumference and endosteal circumference in early puberty (P < .03 for all) and with lumbar spine, whole-body bone mineral content and areal BMD, trabecular and cortical area, and periosteal circumference in late puberty (P < .04 for all). Free testosterone was positively associated with trabecular area and cortical thickness, and total testosterone was positively associated with trabecular volumetric BMD in late puberty (P < .03 for all).

Estradiol was positively associated with whole-body bone mineral content, trabecular area and periosteal circumference in early puberty (P < .05 for all); lumbar spine and whole-body bone mineral content and areal BMD, trabecular and cortical density, cortical area and cortical thickness (P < .05 for all). Free estradiol was negatively associated with endosteal circumference during prepuberty (P < .001) and positively associated with cortical area in early and late puberty (P < .002 for both).

IGF-I was positively associated with height and trabecular area in prepuberty and early puberty (P < .046 for all), whole-body areal BMD, cortical area, density and thickness in prepuberty (P < .05 for all) and periosteal and endosteal circumference in early puberty (P < .04 for both). IGF-I was negatively associated with cortical area in late puberty.

“Our data once again emphasize the major role of adequate sex steroid exposure for optimal skeletal development during puberty,” the researchers wrote. “Whereas estradiol exposure was most strongly associated with bone mineralization, testosterone levels were related to parameters of bone size. Hence, evaluation of sex steroid status, in addition to measurement of classical bone turnover markers, should be considered for the biochemical evaluation of bone metabolism in peri-pubertal boys.”