Bone loss in patients with untreated chronic obstructive pulmonary diseaseis mediated by an increase in bone resorption associated with hypercapnia

This study sought to determine whether the bone loss in untreated chronic o bstructive pulmonary disease (COPD) is associated with hypercapnia and/or r espiratory acidosis. Bone mineral density (BMD) measured at the distal fore arm of the nondominant arm (with peripheral quantitative computed tomograph y [pQCT]) and serum markers of bone turnover were determined in 71 male pat ients with untreated COPD and 40 healthy male subjects who matched the pati ents in age, weight, and body mass index (BMI). The COPD patients, compared with controls, had reduced pulmonary functions, lower arterial pH, and ele vated arterial partial pressure of CO2 (P-CO2). The BMD (in T score) was si gnificantly lower in COPD patients than that in control subjects (-1.628 +/ - 0.168 vs. -0.058 +/- 0.157; p < 0.001). The BMD of COPD patients correlat ed positively with arterial pH (r = 0.582; p < 0.001), negatively with P-CO 2 (r = -0.442; p < 0.001), and negatively with serum cross-linked telopepti de of type I collagen (ICTP), a bone resorption marker (r = -0.444; p < 0.0 01) but not with serum osteocalcin, a bone formation marker. Serum ICTP, bu t not osteocalcin, correlated with P-CO2 (r = 0.593; p < 0.001) and arteria l pH (r = -0.415; p < 0.001). To assess the role of hypercapnia, COPD patie nts were divided into the hypercapnic (P-CO2 > 45 mm Hg; n = 35) and eucapn ic (P-CO2 = 35-45 mm Hg) group (n = 36). Patients with hypercapnia had lowe r BMD, lower arterial pH, and higher serum ICTP than did patients with euca pnia. Arterial pH and serum ICTP of eucapnic patients were not different fr om those of controls. To evaluate the role of uncompensated respiratory aci dosis, COPD patients with hypercapnia were subdivided into those with compe nsatory respiratory acidosis (pH greater than or equal to 7.35; n = 20) and those with uncompensated respiratory acidosis (pH < 7.35; n = 15). The BMD and serum ICTP were not different among the two subgroups. In conclusion, this study presents the first associative evidence that the bone loss in CO PD is at least in part attributed to an increased bone resorption that is a ssociated primarily with hypercapnia rather than uncompensated respiratory acidosis.