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- Grundberg, Elin, et al.
(författare)
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The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism.
- 2007
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:6, s. 2300-6
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ERalpha cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERalpha function in the presence of estrogen. OBJECTIVE: The objective of the study was to determine whether a RIZ P704 insertion (+)/deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. DESIGN: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmö OPRA Study, respectively. SETTING: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmö University Hospital, and Uppsala University Hospital. PARTICIPANTS: In total, 4058 men and women, aged 69-81 yr, were randomly selected from population registries. MAIN OUTCOME MEASURES: BMD (grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. RESULTS: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(-/-) group (r = 0.19 vs. r = 0.08, P < 0.05). CONCLUSIONS: These large-scale studies of elderly men and women indicate that the ERalpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.
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| 2. |
- Holmberg, Anna H, et al.
(författare)
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The Association Between Hyperglycemia and Fracture Risk in Middle Age. A prospective, population-based study of 22 444 men and 10 902 women.
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 93:3, s. 815-822
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Type 1 diabetes mellitus is associated with increased fracture risk, whereas the risk associated with type 2 diabetes is less obvious. Elevated fasting blood glucose (FBG) and high 2-hour glucose during an oral glucose tolerance test (OGTT) indicate impaired glucose tolerance or diabetes. The associations between FBG, 2-h glucose and the risk of fracture were investigated. Methods: The Malmö Preventive Project consists of 22 444 men (44 +/- 6.6 yrs) and 10 902 women (50 +/- 7.4 yrs), with a follow-up of 19 (+/-3.9)years and 15 (+/-4.5) years for incident fractures. Baseline assessment included multiple examinations and lifestyle information. A logistic regression model was used. Adjustments were made for age, BMI, and smoking. Results: Low-energy fractures were recorded in 1246 men and 1236 women. A 2-h glucose measurement between 4.3 and 6.2 mmol/L in men (2(nd) and 3(rd) quartiles), and above 6.5 mmol/L in women (3(rd) and 4(th) quartiles), adjusted for age, BMI, and smoking, was significantly associated with decreased risk of multiple fractures, in men (ORs 0.57-0.71) and women (ORs 0.38-0.66). In women, a 2-h glucose measurement above 7.5 mmol/L was associated with a decreased risk of osteoporotic fractures (OR 0.57, CI 95% 0.44-0.74). Conclusions: In middle-aged men and women, elevated 2-h glucose levels were associated with decreased risks of multiple and osteoporotic fractures, independent of age, BMI, and smoking. A high 2-h glucose level is characterized by peripheral insulin resistance with a high insulin level. Our findings indirectly suggest a positive effect on bone from hyperglycemia.
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