A team of researchers of MedUni Vienna working with the endocrinologists and gender physicians Michael Leutner and Alexandra Kautzky-Willer as well the division for complex statistical systems with Peter Klimek and Caspar Matzhold in cooperation with Complexity Science Hub Vienna were able to demonstrate for the first time a connection between the potency and dosage of statins with a diagnosis of osteoporosis, based on several million data sets. Essential result: the higher the dosage, the greater the likelihood of osteoporosis. The study was published in the top journal "Annals of the Rheumatic Diseases".
In the past, the focus in the research of statins was primarily in the area of prevention and treatment of cardiovascular diseases. It is scientifically proven that statin therapies lead to a significant risk reduction or cardiovascular events due to the cholesterol-reducing effect. The revolutionary results of statin in the prevention and therapy of cardiovascular diseases achieved that the target values of LDL cholesterol in high-risk patients was reduced to below 55 mg/dl by the specialist association. However, hardly any research had been done on the extent of the effect of these low concentrations of cholesterol on the composition of vital hormones, such as sex hormones, and the associated illnesses such as osteoporosis.
Statins generally ensure a selective inhibition of the 3-Hydroxy-3Methyl-Glutarat-CoA-reductase (HMG-CoA-reductase). This results in a limited cholesterol composition and allows for the therapeutic reduction of the cholesterol level. Kautzky-Willer: "Cholesterol is the basic element for the composition of sex hormones such as oestradiol and testosterone, but also of mineralocorticoids and glucocorticoids such as aldosterone and cortisol. Earlier studies show that low concentrations of sex hormones - here particularly the reduction of estrogen in the menopause - are substantially responsible for the increase of osteoporosis in women. This is mainly caused by the fact that the low concentrations of estrogen lead to increased bone resorption, thus reducing the bone mineral density. A similar relationship with the bone density could be found also in case of testosterones."
Based on this biochemical background, the relationship of variously potent statins and their dosages with the diagnosis of osteoporosis were examined. "From the medical data of more than 7.9 million Austrians from 2006 to 2007m we have filtered out those who regularly took statins over a period of at least one year", explains Caspar Matzhold (MedUni Wien and Complexity Science Hub Vienna/CSH), who was responsible for the processing and statistical analysis of the data in this study. From this, we were able derive the daily dosage of statins and form various dosage groups." The groups with a lower statin dosage produced a lesser than expected number of osteoporosis for this population group, so Michael Leutner, Lead Author of the study: "Dosages up to 10 mg of the conventional active ingredients such as Lovastatin, Pravastatin, Simvastatin or Rosuvastatin were associated with a lower risk of an osteoporosis diagnosis compared to those patients who had not received a statin therapy."
Higher dosage, more osteoporosis cases
Alexandra Kautzky-Willer, Head of the study and corresponding author, adds:
Interestingly, however, the tide turns from a dosage of 20 mg for Simvastatin, Atorvastatin and Rosuvastatin - upward of these dosages, we found an excessive presentation of osteoporosis cases in the statin group. This trend remains also once the increased osteoporosis risk due to excessive weight and other previous illnesses had been extrapolated."
The results were substantiated in a gender-specific analysis which resulted in a similar dosage dependency of statins with the diagnosis of osteoporosis in both genders.
New insight due to interdisciplinary cooperation
"It is possible that the more effective reduction of cholesterol under greater dosages of statins could lead to a more potent inhibition of the composition of sex hormones and thus an increase bone resorption, which could possibly result in a reduction of the bone mineral density", explain the authors. "We have already seen in earlier studies how helpful such large data sets are to verify medical hypotheses", comments Peter Klimek, Head of the Data Analysis Team at MedUni Vienna and CSH.
"The close cooperation between the experts with medical expertise and us, who are versed in the methodical knowledge to handle big data, results in entirely new insights." This permits the following conclusion: Particularly high-risk patients for osteoporosis, such as post-menopausal women undergoing statin therapy, should be subjected to regular controls of the bone metabolism. With these new results, science has come a considerable step closer to personalized and individualized medicine. The study was supported by the WWTF (MA16-045).
Leutner, M. et al. (2019) Diagnosis of osteoporosis in statin-treated patients is dose-dependent. Annals of the Rheumatic Diseases. doi.org/10.1136/annrheumdis-2019-215714.