In the Journals

Low bone turnover markers predict cancer risk in postmenopausal women

In a large cohort of postmenopausal women, low levels of bone turnover markers predicted increased cancer risk independent of bone mineral density and other known cancer risk factors, according to findings published in Bone.

Cecile Liv Bager, PhD, team leader at ProScion in Herlev, Denmark, and colleagues analyzed data from 5,855 postmenopausal Danish women enrolled in the Prospective Epidemiologic Risk Factor (PERF) study, established in 1999-2001 to identify risk factors for age-related diseases (mean age at baseline, 71 years). Participants provided baseline fasting blood samples to measure the bone turnover markers C-terminal telopeptide of type 1 collagen (CTX) and osteocalcin, and underwent spine, femur and whole-body BMD measurements via DXA. Cancer diagnoses were obtained from the Danish Cancer Registry. Researchers used Cox hazard regression models with age as a timescale to estimate the association between bone measures and cancer risk at 3, 6 and 12 years of follow-up.

Within the cohort, 252 women developed cancer after 3 years of follow-up, 462 developed cancer after 6 years of follow-up, and 881 developed cancer after 12 years of follow-up. Researchers found that measurements of osteocalcin were lower in cases vs. non-cases (mean, 29.4 ng/mL vs. 30.77 ng/mL; P = .004), as were measurements of CTX (mean, 0.42 ng/mL vs. 0.45 ng/mL; P = .001). There were no between-group differences in calcium measurements, femur BMD, whole-body BMD or the number of patients prescribed bisphosphonates, according to researchers.

In the adjusted model, CTX (HR = 0.82; 95% CI, 0.76-0.96) and osteocalcin (HR = 0.75; 95% CI, 0.62-0.9) were predictors of cancer at 3 years of follow-up independent of other bone measures and cancer risk factors, the researchers reported.

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In a large cohort of postmenopausal women, low levels of bone turnover markers predicted increased cancer risk independent of bone mineral density and other known cancer risk factors.
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In analyses stratified by site-specific cancers, researchers found that lower levels of CTX and osteocalcin were associated with increased risk for all types of cancer.

“How bone turnover is associated with cancer risk requires further investigation, but several potential mechanisms are worthy of consideration,” the researchers wrote. “A minimal remodeling is necessary to repair old and damaged cells, release growth factors and maintain tissue integrity. We have previously shown that a balanced turnover of both bone and soft tissue is associated with a decreased risk of mortality. Women in the lowest and highest quintile of CTX and osteocalcin had a two times increased risk of mortality compared to women in the middle quintile, highlighting the importance of a healthy [extracellular matrix] balance.”

The researchers noted that in light of the findings, it is possible that a decrease in bone turnover is a sign of a decline in tissue regenerative potential and a “mirror of general health.” – by Regina Schaffer

Disclosures: Two of the study authors report they are employees of ProScion. Please see the study for all other authors’ relevant financial disclosures.

In a large cohort of postmenopausal women, low levels of bone turnover markers predicted increased cancer risk independent of bone mineral density and other known cancer risk factors, according to findings published in Bone.

Cecile Liv Bager, PhD, team leader at ProScion in Herlev, Denmark, and colleagues analyzed data from 5,855 postmenopausal Danish women enrolled in the Prospective Epidemiologic Risk Factor (PERF) study, established in 1999-2001 to identify risk factors for age-related diseases (mean age at baseline, 71 years). Participants provided baseline fasting blood samples to measure the bone turnover markers C-terminal telopeptide of type 1 collagen (CTX) and osteocalcin, and underwent spine, femur and whole-body BMD measurements via DXA. Cancer diagnoses were obtained from the Danish Cancer Registry. Researchers used Cox hazard regression models with age as a timescale to estimate the association between bone measures and cancer risk at 3, 6 and 12 years of follow-up.

Within the cohort, 252 women developed cancer after 3 years of follow-up, 462 developed cancer after 6 years of follow-up, and 881 developed cancer after 12 years of follow-up. Researchers found that measurements of osteocalcin were lower in cases vs. non-cases (mean, 29.4 ng/mL vs. 30.77 ng/mL; P = .004), as were measurements of CTX (mean, 0.42 ng/mL vs. 0.45 ng/mL; P = .001). There were no between-group differences in calcium measurements, femur BMD, whole-body BMD or the number of patients prescribed bisphosphonates, according to researchers.

In the adjusted model, CTX (HR = 0.82; 95% CI, 0.76-0.96) and osteocalcin (HR = 0.75; 95% CI, 0.62-0.9) were predictors of cancer at 3 years of follow-up independent of other bone measures and cancer risk factors, the researchers reported.

#
In a large cohort of postmenopausal women, low levels of bone turnover markers predicted increased cancer risk independent of bone mineral density and other known cancer risk factors.
Adobe Stock

In analyses stratified by site-specific cancers, researchers found that lower levels of CTX and osteocalcin were associated with increased risk for all types of cancer.

“How bone turnover is associated with cancer risk requires further investigation, but several potential mechanisms are worthy of consideration,” the researchers wrote. “A minimal remodeling is necessary to repair old and damaged cells, release growth factors and maintain tissue integrity. We have previously shown that a balanced turnover of both bone and soft tissue is associated with a decreased risk of mortality. Women in the lowest and highest quintile of CTX and osteocalcin had a two times increased risk of mortality compared to women in the middle quintile, highlighting the importance of a healthy [extracellular matrix] balance.”

The researchers noted that in light of the findings, it is possible that a decrease in bone turnover is a sign of a decline in tissue regenerative potential and a “mirror of general health.” – by Regina Schaffer

Disclosures: Two of the study authors report they are employees of ProScion. Please see the study for all other authors’ relevant financial disclosures.