Ethnic differences in levels of bone and cartilage biomarkers and hormonal responsiveness in nine groups of postmenopausal Asian women: the Pan-Asia Menopause (PAM) study.
OBJECTIVE
Significant differences in baseline lipid and reproductive hormone profiles and in responsiveness of lipids to hormone therapy (HT) have previously been found among nine ethnic groups of Asian postmenopausal women participating in the Pan-Asia Menopause (PAM) study. Based on these findings, the primary objective of this study was to test the hypothesis that biomarkers of bone turnover and cartilage degradation and their responsiveness to HT differ among the ethnic groups.


METHODS
The PAM study was a prospective, randomized, double-blind clinical trial evaluating 1028 postmenopausal women at 22 clinical centers in 11 Asian countries/territories. Subjects were randomized to one of three continuous combined conjugated estrogens (CE)/medroxyprogesterone acetate (MPA) doses: CE/MPA (in mg/day) = 0.625/2.5; 0.45/1.5; and 0.3/1.5. Following baseline evaluations, subjects received therapy for six continuous 28-day cycles (6 months). Biomarkers for bone resorption (alphaalphaCTX and betabetaCTX, representing newly synthesized and old bone, respectively), bone formation (osteocalcin) and cartilage degradation (CTX-II) were analyzed centrally by state-of-the-art methods.


RESULTS
The baseline concentrations of the four biomarkers were significantly associated with ethnicity. This association was independent of age and body mass index (BMI). The biomarker levels varied widely among the ethnic groups, showing ranges of alphaalphaCTX = 0.78-1.14 microg/mmol for Taiwanese vs. Malay women; betabetaTCX = 3.77-4.85 microg/mmol for Korean vs. Pakistani women; osteocalcin = 14.9-24.9 microg/l for Korean vs. Pakistani women; and CTX-II = 300-479 microg/mmol for Vietnamese vs. Indonesian women. The baseline biomarker levels were significantly and independently affected by BMI, but not by age. There was a weak but consistent negative correlation between baseline estradiol levels and baseline biomarkers. Hormone therapy for 6 months significantly lowered the biomarker levels in all ethnic groups, with a few exceptions for CTX-II in the lowest dose group. Ethnicity, but not age or BMI, was significantly associated with the response of the bone markers, whereas ethnicity, age and BMI were significantly associated with the response of the cartilage degradation marker.


CONCLUSIONS
Baseline levels and hormonal responsiveness of two bone resorption markers, a bone formation marker, and a marker of cartilage degradation differ among the ethnic groups of Asian postmenopausal women evaluated in this study. The clinical significance of these findings remains to be investigated.
Holinka
C F
CF
PharmConsult, New York, NY, USA.
Christiansen
C
C
Tian
X W
XW
Ausmanas
M K
MK
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001208:Asia / Q000208:ethnology; D044466:Asian People; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005006:Ethnicity; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000378:metabolism; D017698:Postmenopause; D011446:Prospective Studies; D016896:Treatment Outcome; D016387:Women's Health
D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II; D004966:Estrogens, Conjugated (USP); D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D017258:Medroxyprogesterone Acetate