BackgroundSymptomatic knee osteoarthritis is a highly age and sex associated complex disease. Little is known about the causes behind this age and sex associated increase, or if genetic and environmental factors impacts differently by gender. Our study examined the risk and heritability of primary knee osteoarthritis leading to total knee arthroplasty and whether these differences were attributable to sex and age differences in heritability.MethodsAll twins of known zygosity from The Danish Twin Register alive in 1997 were examined in a nationwide population based follow-up study collecting information on all twins recorded in The Danish Knee Arthroplasty from 1997 to follow-up in 2010. Our main outcomes were the cumulative incidence, probandwise concordance rates, heritability, within pair correlations in monozygotic and dizygotic twin pairs and the genetic and environmental influence estimated in models taking into account that individuals may not have had a total knee arthroplasty at follow up.Results92,748 twins were eligible for analyses and 576 twins had a record of primary knee osteoarthritis in The Danish Knee Arthroplasty Register at follow-up comprising 358 female and 218 male twin cases. The risk increased particular after the age of 50 years displaying significant sex differences in the elderly. In the sex stratified analyses a discrete genetic component was found in females, but in males no genetic component could be detected. In both genders common and unique environmental factors were highly significant. In the sex-adjusted analysis an additive genetic component of 18 % (0; 62), a shared environmental component of 61 % (25; 97) and an individual environmental component of 21 % (6; 36) accounted for the variation in liability to primary total knee arthroplasty.ConclusionThe risk of primary total knee arthroplasty increases significantly after the age of 50 years, in particular in females, displaying significant sex differences in the elderly. After sex-adjustment 82 % of the variation in liability to primary total knee arthroplasty was attributable to common and unique environmental factors; the remaining 18 % of this variation was attributable to additive genetic factors indicating a pivotal impact of environmental factors on this disease.

IntroductionPrimary hip osteoarthritis, radiographic as well as symptomatic, is highly associated with increasing age in both genders. However, little is known about the mechanisms behind this, in particular if this increase is caused by genetic factors. This study examined the risk and heritability of primary osteoarthritis of the hip leading to a total hip arthroplasty, and if this heritability increased with increasing age.MethodsIn a nationwide population-based follow-up study 118,788 twins from the Danish Twin Register and 90,007 individuals from the Danish Hip Arthroplasty Register for the period 1995 to 2010 were examined. Our main outcomes were the cumulative incidence, proband-wise concordance and heritability on age, within-pair correlations in monozygotic and dizygotic twin pairs, and the genetic and environmental influence estimated in models taking into account that individuals may not have had a total hip arthroplasty at the time of follow-up.ResultsThere were 94,063 twins eligible for analyses, comprising 835 cases of 36 concordant and 763 discordant twin pairs. The probability increased particularly from 50 years of age. After sex and age adjustment a significant additive genetic component of 47 % (12:79), a shared environmental component of 21 % (2:76) and a unique environment component of 32 % (21:41) accounted for the variation in population liability to total hip arthroplasty. The sex-adjusted proband-wise concordance and heritability on age indicated an increasing age-associated genetic influence onwards from 60 years of age.ConclusionThe cumulative incidence in primary hip osteoarthritis leading to total hip arthroplasty increases in particular after the age of 50 years in both genders. Family factors of genes and shared environment are highly significant and account for 68 % of the variation in the population liability to total hip arthroplasty; however, the genetic influence increases significantly from 60 years of age onwards.

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Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium metabolism and biochemical markers of bone turnover were investigated in 12 healthy male volunteers in a randomized, placebo-controlled, cross-over design. The nasal spray was given in the morning, and subsequently blood and urine samples were collected for 26 hours. There was a significant decrease in serum ionized calcium with a nadir 4 hours after administration of nasal SCT accompanied by a significant increase in serum parathyroid hormone (P = 0.01) and serum calcitriol (P = 0.04). Nasal SCT did not reduce urinary hydroxyproline/creatinine. Urinary deoxypyridinoline/creatinine was lowered significantly 2 hours after administration of nasal SCT and throughout the first 24 hours, but remained unchanged for the last 2 hours. On a 24-hour basis, urinary deoxypyridinoline/creatinine decreased from 14.1 (3.5) nmol/mmol to 11.7 (3.2) nmol/mmol after nasal SCT (P = 0.04). Nasal SCT did not change the serum levels of alkaline phosphatase, osteocalcin, and the carboxyterminal propeptide of type 1 procollagen. The results indicate that nasal SCT given as a single dose provokes a modest decrease in bone resorption lasting several hours, but leaves bone formation unaffected.