Osteoporosis and autoimmune inflammation
Most readers here are well aware that osteoporosis results from a failure to maintain the resilient protein matrix (web, or 'scaffolding') of bone tissue, and that chronic inflammation is a prime contributor. A paper just published in Current Opinion in Endocrinology, Diabetes and Obesity examines the role of autoimmunity, now so widespread, in skeletal disease in general and osteoporosis in particular. The authors state:
"There is an increased risk of osteoporotic fractures and osteonecrosis often at a young age among patients with certain systemic autoimmune diseases. The loss of bone mineral density and bone integrity seen with these diseases often cannot be explained by traditional risk factors alone..."
The review studies that document that in rheumatoid arthritis the risk of osteoporosis is doubled, the risk for hip fracture is doubled or tripled, and there is a two to six-fold risk of vertebral fracture.
"Reduction in bone mineral density in RA may be influenced by immobility, inflammation associated with osteoclast activation, and medications used to treat the disease such as corticosteroids."
In the case of lupus...
"Risk factors for osteoporosis in patients with SLE include high disease activity, vitamin D deficiency, renal disease, corticosteroid use, and premature ovarian failure from cytotoxic medications..."
The include a review of vitamin D in skeletal health and note that besides its well-known role in bone metabolism...
"...vitamin D is thought to have an immunomodulatory function, with deficient levels associated with impaired innate immune function and overexuberant adaptive immune function. Markers of inflammation have been associated with increased bone turnover and bone loss, a factor that is thought to be particularly at play among patients with inflammatory diseases. Consequently, low vitamin D levels can lead to accelerated bone loss among patients with inflammatory diseases. Put together, these observations move us beyond the calcitropic effects of vitamin D deficiency among patients with inflammatory diseases, and argue in favor of higher serum levels than are currently accepted."
Importantly, the mechanisms by which inflammation disrupts skeletal are becoming known:
"Several studies have found an association between pro-inflammatory cytokines which play a role in bone resorption, such as TNF-α, IL-1 and IL-6, and the development of osteoporosis. Epidemiologic studies have shown levels of systemic inflammation to predict bone loss and future fracture. It is becoming clear that T cells play a pivotal role in regulating bone homeostasis through direct interactions with bone marrow, stromal cells and osteoblasts. Once activated, these T cells release osteoclastogenic cytokines and Wnt ligands."
And it appears that steroid treatment does not undo the skeletal effects of inflammation:
"Among a cohort of 20 patients with SLE who had never been on steroids, osteocalcin levels were significantly lower, the urinary excretion of cross-links were significantly higher than in a non-SLE cohort, suggesting that there is decreased bone formation and increased bone resorption among steroid-naive SLE patients. Although these findings were attributed to the underlying disease, comparable results were detected among a steroid-treated cohort implying that steroid treatment does not undo the skeletal effects of inflammation in SLE as was speculated by some researchers."
Summing up the studies linking osteoporosis to SLE, the authors state:
"These findings suggest that patients with more active inflammation are at greater risk for bone loss."
Concerning the importance of vitamin D and autoimmunity, they comment:
"In light of the alarming prevalence of vitamin D deficiency seen worldwide, all patients with autoimmune disease should have at least a baseline screening 25-hydroxyvitamin level to screen for vitamin D deficiency. The only laboratory test usually required to ascertain the patient's status is the 25-hydroxyvitamin D level with a goal of at least greater than 30 ng/ml."
Their conclusion is heightened in significance by the sharp increase in autoimmune disorders in recent years:
"Bone loss and damage commonly occurs in patients with systemic autoimmune diseases. We are improving in our ability to diagnose and treat autoimmune diseases and their complications; yet osteoporosis and osteonecrosis remain growing comorbid conditions."