High dose statins can increase osteoporosis risk finds Annals of the Rheumatic Diseases study

A higher dose of statins, the cholesterol-lowering drug, could increase the risk of osteoporosis,  a recent has found. However, at low doses statins provide protection against bone resorption.
According to the study, whether statins decrease or increase the risk of osteoporosis is dependent on their dosage. At low doses, statins provide protection against bone resorption. However, the higher the dosage of statins greater is the risk of osteoporosis. In short, osteoporosis is underrepresented in low-dose and over-represented in high-dose statin treatment. Findings are based on an analysis of millions of patient data.

Osteoporosis is one of the most commonly occurring metabolic bone disorders. It is characterised by decreased bone mineral density (BMD) in which bones become weak and brittle. This increases the bone fragility making it susceptible to fracture.

Statins are cholesterol-lowering drugs that help the heart and brain by preventing artery plaques- buildups of cholesterol, calcium and other substances in blood vessels-- from blocking blood flow and causing a heart attack or stroke. They are among the most prescribed drugs worldwide.

Whether HMG-CoA-reductase inhibition, the main mechanism of statins, plays a role in the pathogenesis of osteoporosis, is not entirely known so far. Researchers conducted the study to investigate the relationship of different kinds and dosages of statins with osteoporosis, hypothesising that the inhibition of the synthesis of cholesterol could influence sex-hormones and therefore the diagnosis of osteoporosis.

Statins inhibit the synthesis of cholesterol from the liver. This lowers blood cholesterol. However, cholesterol is crucially important for many processes in the body. Among other things, it is a basic building block for the production of sex hormones such as estradiol and testosterone.

For the investigation, the researchers used Big Data. They obtained access to the health data of more than 7.9 million Australians between 2006-2007. From this big data set the patients who regularly took statins for at least one year were filtered out. The researchers also calculated the daily dosage of statins and formed different dosage groups. In a further step, the interdisciplinary team filtered out osteoporosis diagnoses.

Key findings of the study include-
* statin treatment was associated with an over-representation of diagnosed osteoporosis compared with controls.
* there was a highly non-trivial dependence of statin dosage with the ORs of osteoporosis.
* Osteoporosis was underrepresented in low-dose statin treatment ) 0-10mg per day) including lovastatin, pravastatin, simvasatin and rosuvastatin.

The exceeding of the 40 mg threshold for simvastatin and the exceeding of a 20 mg threshold for atorastatin and for rosuvastatin was related to an over-representation of osteoporosis.

We know that low concentrations of sex hormones- especially the drop in estrogen levels during menopause-- are the main cause for the increase of osteoporosis in women, explains a Dr.  There is a similar relationship between bone density and testosterone. We were interested in whether the inhibition of cholesterol production by statins has an effect on bone formation and whether there could be a dose-response relationship.

In the lower dose groups, there were fewer osteoporosis cases than expected, points out the Dr. At doses up to 10mg of the statins lovastatin, pravastatin, simvastatin or rosuvastatin, the scientists found fewer osteoporosis diagnoses compared to patients without statin therapy. With doses of 20 mg, and more, however,  this seems to turn. We found more osteoporosis cases in patients treated with simvastatin, atorvastatin and rosuvastatin than expected, explains the Dr. The higher the dosage, the stronger the effect.

In earlier, joint studies we saw how helpful large data sets can be to examine open medical questions, says the leader of the study. The combination of medical expertise with our knowledge in big data analysis makes completely new insights possible. According to the researcher, the newly discovered correlation between statin therapy and osteoporosis risk should now be investigated in clinical studies.

With such results, we're coming closer to truly personalised and individualised medicine, maintains the Dr. We can now advise high-risk osteoporosis patients undergoing statin therapy to have their bone metabolism regularly monitored.

We propose that monitoring high-risk patients, that is postmenopausal female patients under high-dosage statin therapy, might be useful in order to offer individual therapy to prevent or treat osteoporosis. This, larger and prospective studies with a focus on dosages of statins should be conducted in order to clarify the relationship with osteoporosis, concluded the authors.
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Omega-3 fatty acid effectively lowers high triglycerides

Omega-3 fatty acid medication reduces triglyceride levels by 20-30% among the majority of people who require treatment for high triglyceride levels, suggests a study.

From our review of the evidence from 17 randomised, controlled clinical trials on high triglyceride levels, we concluded that treatment with 4 gm daily of any of the available prescription choices is effective and can be used safely in conjunction with statin medicines that lower cholesterol, said an author of the study.

There are 2 prescription omega-3 fatty acid medications available. One combines 2 types of fatty acids, EPA ( eicosapentaenoic acid) and DHA ( docosahexaenoic acid). The other medication provides EPA only. Since there have been no head-to-head comparisons of the 2 formulations at prescription dosing, the advisory does not recommend one over the other.

Triglycerides are fats that circulate in the blood. Some studies have shown that elevated levels of triglycerides ( above 200mg/dL) can lead to atherosclerosis ( narrowing of the arteries), which increases the risk of heart attack and stroke. In addition to cardiovascular risk,  very high levels of triglycerides ( above 500mg.dL) can also cause pancreatitis, an inflammation of the pancreas.

A researcher pointed out that people with high triglyceride levels should not try to treat the condition themselves with non-prescription, omega-3 fatty acid fish oil supplements.

Dietary supplements containing omega-3 fatty acids are not regulated by the FDA, They should not be used in place of prescription medication for the long-term management of high triglycerides, he said.

The effective dose for prescription omega-3 fatty acids is 4 gm per day taken with food. Currently, the FDA has approved prescription omega-3 fatty acid medications only for treating very high triglyceride levels above 500 mg/dL.

Fish is a good source of omega-3 fatty acids and the American Heart Association recommends eating  fatty fish-such as salmon, mackerel, herring and albacore tuna- at least twice per week.

In the analysis of the current scientific data, the advisory panel found that most people with high triglycerides ( 200-490 mg/dL), prescription doses of omega-3 fatty acids using drugs with either EPA+DHA or EPA alone can reduce triglyceride by 20-30%.

Contrary to common perception, the formula that contains both EPA and DHA does not increase the " bad" form of cholesterol (LDL-C) among most people with high triglyceride levels (200-499 mg/dL). However, when the drug is given to people with very high triglyceride levels at 500 mg/dL or greater, LDL-C may increase.

The panel's review found that prescription omega-3 drugs are effective in reducing triglyceride levels regardless of whether people are on statin therapy.

In a recent large, randomized placebo-controlled study called REDUCE-IT, researchers found that the EPA-only medication combined with statin medication resulted in a 25 % reduction in major cardiovascular events ( heart attack, stroke and cardiovascular death) among people with high triglycerides.

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