ORADE 2018: WCO-IOF ESCEO Conference April/2018. Krakow Poland.
Thank you to ORADE for the opportunity to attend this international meeting about Osteoporosis, Osteoarthritis, and Sarcopenia. Many of the presentations provided interesting European perspectives on treatments of these chronic MSK diseases, plus information about Iatrogenic Osteoporosis and Breast Cancer Bone Targeting Agents. These learnings will be applicable in my clinical practice.
Mediterranean Diet and Musculoskeletal Diseases:
(N. Veronese, Italy) The Mediterranean Diet (rich in grains, vegetables, fruit, beans, olive oil, seeds and fish, and lower in dairy and fatty meats) has anti-oxidant and anti-inflammatory properties previously recognized to be beneficial for many chronic diseases. The Med diet has been associated with decreased joint inflammation in Rheumatoid Arthritis. Recent epidemiologic studies report a lower prevalence of Osteoarthritis with the Med diet. The combination of Med diet, physical activity and calcium restriction may lower inflammation and decrease risks for Osteoarthritis such as obesity. (S. Maggi, Italy) The Med diet is also associated with decreased fracture risk—the WHI reported a 20% decrease in hip fractures and other studies have reported similar findings in men and women. It is believed that olive oil has a positive effect on bone metabolism. Conclusion: The Med diet is beneficial in Osteoarthritis and Osteoporosis.
Gut microbiota and Osteoporosis:
“Microbiota and Bone Disease” (R. Rizzoli, Switzerland) Gut microbiota varies with age, sex, genetic background, living conditions, diet, and is also affected by travel, illness, and drugs. Microbiota metabolism affects the gastrointestinal tract–permeability, nutrient absorption and immunity; and thereby has been linked to bowel cancer, obesity, diabetes, and gi inflammatory, autoimmune, neurologic and psychiatric diseases. Calcium and Vitamin D may alter gut microbiota. Fermented dairy products (eg yogurt) contain probiotics and yogurt consumers have decreased radius bone loss independent of other factors; also a study in Ireland found increased yogurt consumption associated with increased BMD and physical function in older adults. PPIs, statins, antibiotics and other drugs may negatively affect BMD and Osteoporosis through effects on the gut microbiota. “Effect of Lactobacillus Reuteri on Bone Loss in Older Women with Low BMD: a RCT” (G. Nilson, Sweden) The ELBOW study randomized patients to receive Lactobacillus Reuteri (probiotic) supplement or placebo for 12 months. Small study numbers, however tibial BMD loss was decreased compared to controls. Conclusion: Yogurt and probiotic supplements decrease bone loss.
“Vitamin D—What is Good and What is Bad?” (B. Dawson-Hughes USA) Vitamin D supplementation in deficient patients has been associated with improved muscle strength and balance. But studies of Vitamin D supplementation and falls have given mixed results–either null effect or up to 15-20% reduction in falls. Two meta-analyses of Vitamin D and fractures have reported contradictory results. These differences may be due to varying entry Vitamin D levels, supplement dose, scheduling and compliance. A study of annual, high dose Vitamin D increased falls and fractures, and studies of monthly dosing of Vitamin D (24,000 units/month) reported increased falls compared to equivalent daily dosing (800 units/day). Therefore Vitamin D dosing and fall risk is a U shaped curve. Similarly there is a reverse J curve for Vitamin D levels and falls and all-cause mortality. Vitamin D supplement has been shown to decrease asthma and respiratory tract infections in older adults in LTC. But a meta-analysis of 3 trials found that Vitamin D has no effect on Osteoarthritis. Conclusion: Vitamin D is not recommended for monthly, yearly or loading doses. Optimal dose of Vitamin D is (still) 800 to 1000U/day. Vitamin D supplement is most beneficial in reducing falls and fractures in those with low Vitamin D levels; other benefits of Vitamin D are in asthma and respiratory infections in select populations. Higher Vitamin D levels are associated with adverse effects.
“Calcium: What is Good and What is Bad? (N. Harvey, UK) The literature suggests that Calcium with Vitamin D leads to a modest reduction in fracture risk, particularly in institutionalized individuals compared to community dwellers. Calcium alone is not supported for this indication. Previously the WHI and a meta-analysis reported a possible weak association of Calcium supplement and myocardial infarction, however the current evidence does not support increased CVS risk with combination Calcium and Vitamin D or dietary calcium. Conclusion: Calcium with Vitamin D supplementation is recommended for individuals who are at risk for dietary insufficiency and those receiving treatment for Osteoporosis. Calcium supplement should be used only to make up a “dietary gap”, and with Vitamin D.
Breast Cancer and Bone Disease:
“Treatment of Metastatic Bone Disease in Women with Breast Cancer” (J. Body, Belgium) In patients with Breast Cancer, bone metastases can result in serious adverse events and the bone targeting agents (BTAs) bisphosphonates and denosumab are effective in reducing this morbidity. Therefore it is recommended to consider a BTA if bone metastases are present even if asymptomatic and continue indefinitely. In addition, a Cochrane meta-analysis of bisphosphonates in breast cancer patients found decreased risk of bone metastases and mortality. Conclusion: bisphosphonates and denosumab decrease morbidity from breast cancer bone metastases. Bisphosphonates should be prescribed for breast cancer patients with an Osteoporosis indication.
Aromatase Inhibitors, Glucocorticoids and Osteoporosis:
“Management of Iatrogenic Osteoporosis” (P. Hadju, Germany) Aromatase Inhibitors (AIs) for breast cancer treatment are associated with decreased BMD and increased risk of fracture through the inhibition of endogenous estrogen; bone loss is 2-3 times that of age-matched postmenopausal controls; and fractures occur at higher BMD T scores and at younger ages. Use of bisphosphonates or denosumab “up front” with AIs increases BMD and decreases fracture risk. “Risk of Fracture is Associated with Dose, Duration and Recency of Glucocorticoid Exposure” (D. Robinson, UK). A RCT of 16,500 patients with RA, ½ taking glucocorticoids (GCs), followed for 4 years, used “weighted cumulative exposure” to glucocorticoids to assess fracture risk. Results: the duration of exposure to GCs increased fracture risk and most fractures occurred in the first year; GCs taken in the past year increase risk; low dose GCs (5mg/day) for long term (6 months) had less fracture risk than high dose (30 mg/day) for short term (1 month); discontinuation of GCs lowered fracture risk to baseline in 6-12 months. Conclusion: Add Osteoporosis treatment with Aromatase Inhibitors. The dose, duration and recency of glucocorticoid treatment determine fracture risk.
Dr. P. Ciaschini