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Nicolella D.P.,Isis Research Network on Musculoskeletal Health | Nicolella D.P.,Southwest Research Institute | O'Connor M.I.,Isis Research Network on Musculoskeletal Health | Enoka R.M.,Isis Research Network on Musculoskeletal Health | And 20 more authors.
Biology of Sex Differences | Year: 2012

The occurrence of knee osteoarthritis (OA) increases with age and is more common in women compared with men, especially after the age of 50 years. Recent work suggests that contact stress in the knee cartilage is a significant predictor of the risk for developing knee OA. Significant gaps in knowledge remain, however, as to how changes in musculoskeletal traits disturb the normal mechanical environment of the knee and contribute to sex differences in the initiation and progression of idiopathic knee OA. To illustrate this knowledge deficit, we summarize what is known about the influence of limb alignment, muscle function, and obesity on sex differences in knee OA. Observational data suggest that limb alignment can predict the development of radiographic signs of knee OA, potentially due to increased stresses and strains within the joint. However, these data do not indicate how limb alignment could contribute to sex differences in either the development or worsening of knee OA. Similarly, the strength of the knee extensor muscles is compromised in women who develop radiographic and symptomatic signs of knee OA, but the extent to which the decline in muscle function precedes the development of the disease is uncertain. Even less is known about how changes in muscle function might contribute to the worsening of knee OA. Conversely, obesity is a stronger predictor of developing knee OA symptoms in women than in men. The influence of obesity on developing knee OA symptoms is not associated with deviation in limb alignment, but BMI predicts the worsening of the symptoms only in individuals with neutral and valgus (knockkneed) knees. It is more likely, however, that obesity modulates OA through a combination of systemic effects, particularly an increase in inflammatory cytokines, and mechanical factors within the joint. The absence of strong associations of these surrogate measures of the mechanical environment in the knee joint with sex differences in the development and progression of knee OA suggests that a more multifactorial and integrative approach in the study of this disease is needed. We identify gaps in knowledge related to mechanical influences on the sex differences in knee OA. © 2012 Nicolella et al.; licensee BioMed Central Ltd.


Boyan B.D.,Georgia Institute of Technology | Tosi L.L.,Childrens National Medical Center | Coutts R.D.,Isis Research Network on Musculoskeletal Health | Enoka R.M.,Isis Research Network on Musculoskeletal Health | And 10 more authors.
Biology of Sex Differences | Year: 2013

An introduction to the accompanying three papers. © 2013 Boyan et al.; licensee BioMed Central Ltd.


Sluka K.A.,Isis Research Network on Musculoskeletal Health | Sluka K.A.,University of Iowa | Berkley K.J.,Isis Research Network on Musculoskeletal Health | O'Connor M.I.,Isis Research Network on Musculoskeletal Health | And 9 more authors.
Biology of Sex Differences | Year: 2012

People with osteoarthritis (OA) can have significant pain that interferes with function and quality of life. Women with knee OA have greater pain and greater reductions in function and quality of life than men. In many cases, OA pain is directly related to sensitization and activation of nociceptors in the injured joint and correlates with the degree of joint effusion and synovial thickening. In some patients, however, the pain does not match the degree of injury and continues after removal of the nociceptors with a total joint replacement. Growth of new nociceptors, activation of nociceptors in the subchondral bone exposed after cartilage degradation, and nociceptors innervating synovium sensitized by inflammatory mediators could all augment the peripheral input to the central nervous system and result in pain. Enhanced central excitability and reduced central inhibition could lead to prolonged and enhanced pain that does not directly match the degree of injury. Psychosocial variables can influence pain and contribute to pain variability. This review explores the neural and psychosocial factors that contribute to knee OA pain with an emphasis on differences between the sexes and gaps in knowledge. © 2012 Sluka et al.; licensee BioMed Central Ltd.


Boyan B.D.,Isis Research Network on Musculoskeletal Health | Boyan B.D.,Georgia Institute of Technology | Hart D.A.,Isis Research Network on Musculoskeletal Health | Enoka R.M.,Isis Research Network on Musculoskeletal Health | And 10 more authors.
Biology of Sex Differences | Year: 2013

Young female athletes experience a higher incidence of ligament injuries than their male counterparts, females experience a higher incidence of joint hypermobility syndrome (a risk factor for osteoarthritis development), and post-menopausal females experience a higher prevalence of osteoarthritis than age-matched males. These observations indicate that fluctuating sex hormone levels in young females and loss of ovarian sex hormone production due to menopause likely contribute to observed sex differences in knee joint function and risk for loss of function. In studies of osteoarthritis, however, there is a general lack of appreciation for the heterogeneity of hormonal control in both women and men. Progress in this field is limited by the relatively few preclinical osteoarthritis models, and that most of the work with established models uses only male animals. To elucidate sex differences in osteoarthritis, it is important to examine sex hormone mechanisms in cells from knee tissues and the sexual dimorphism in the role of inflammation at the cell, tissue, and organ levels. There is a need to determine if the risk for loss of knee function and integrity in females is restricted to only the knee or if sex-specific changes in other tissues play a role. This paper discusses these gaps in knowledge and suggests remedies. © 2013 Boyan et al.; licensee BioMed Central Ltd.

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