title: Relation of estrogen receptor-alpha gene polymorphism and hormone replacement therapy to fall risk and muscle strength in early postmenopausal women.
abstract: BACKGROUND
  Several factors may increase fracture risk, among them reduced bone mineral density (BMD), increased bone resorption, microarchitectural deterioration of bone, increased fall risk, and decreased muscle strength. We have previously reported that PvuII polymorphism of the estrogen receptor-alpha (ER alpha) gene is associated with bone loss rate, fracture risk, and response to hormone replacement therapy (HRT) in early postmenopausal Finnish women.
  
  
  METHODS
  We studied the influence of the ER alpha genotype on fall risk and muscle strength in a 5-year randomized HRT trial of 331 early postmenopausal women (subgroup of the population-based OSTPRE study, Kuopio, Finland). A 5-year postal inquiry in May 1994 included questions on falls during the previous 12 months. Grip strength was measured with dynamometer. The ER alpha gene polymorphism was analysed using PCR and PvuII restriction enzyme digestion. RESULTS. In all, 97 out of the 331 women reported falls. Half of those (56%) were slip falls, mostly during the winter season. In the HRT group, the ER alpha genotype was associated with fall risk (P = 0.002, logistic regression). The risk of falls (RR) was higher in women with the PP genotype than in those with the Pp (RR = 5.26, 95% CI 1.98-13.94, P = 0.001) or the pp (RR = 3.84, 95% CI 1.46-10.12, P = 0.007) genotype. When the falls were divided into slip (environment-related) and non-slip (endogenous) falls, the non-slip falls were associated with the genotype (P = 0.004), but the slip falls were not so clearly (P = 0.061). When all falls and non-slip falls were adjusted to the number of chronic health disorders and the variable time-since-menopause, the difference between the genotypes persisted (P = 0.003 and P = 0.010, respectively). In the non-HRT group, the ER alpha genotype was not associated with fall risk. The baseline or the 5-year grip strength values were not influenced by the ER alpha genotype. In conclusion, ER alpha polymorphism is associated with fall risk, especially with non-slip falls, in early postmenopausal Finnish women during the HRT. We have previously reported that, during HRT, women with the P allele have decreased fracture risk and that they may preferentially derive benefit from the positive effect of HRT on BMD. This suggests that the influence of ER alpha polymorphism may depend on the target tissue (bone versus the nervous system).
  
  
  CONCLUSIONS
  In these early postmenopausal, non-osteoporotic and relatively healthy women, the increased fall risk associated with the PP genotype was not associated with increased fracture risk, possibly due to improved bone strength during the HRT although falls generally predispose to fractures.
authors.affiliation: Department of Biochemistry, University of Kuopio, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Salmén
authors.forename: Anna-Mari
authors.initials: AM
authors.lastname: Heikkinen
authors.forename: Anitta
authors.initials: A
authors.lastname: Mahonen
authors.forename: Heikki
authors.initials: H
authors.lastname: Kröger
authors.forename: Marja
authors.initials: M
authors.lastname: Komulainen
authors.forename: Seppo
authors.initials: S
authors.lastname: Saarikoski
authors.forename: Risto
authors.initials: R
authors.lastname: Honkanen
authors.forename: Juhani
authors.initials: J
authors.lastname: Partanen
authors.forename: Pekka H
authors.initials: PH
authors.lastname: Mäenpää
mesh_terms: D000058:Accidental Falls / Q000517:prevention & control; D000367:Age Factors; D000368:Aged; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D003720:Densitometry; D005260:Female; D005387:Finland; D005598:Fractures, Spontaneous / Q000453:epidemiology / Q000235:genetics; D018737:Hand Strength / Q000502:physiology*; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011336:Probability; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics*; D012016:Reference Values; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D011960:Receptors, Estrogen