Table of contents
- Method & Results
The study aims to examine the recent researches on the pharmacogenetics of osteoporosis, assess the evaluations conducted on previous researches, give alternatives to availability of drugs, lessen the unpredicted harmful effects and costs of the current drugs, and enhance the human life.
Method & Results
The demineralization of bone, reduced bone mass and normal bone micro-architecture alteration are the primary causes of osteoporosis, a condition most often found in elders. Pharmacotherapy for osteoporosis targets to lessen fractures through reducing the rate of bone absorption or forming new bone.
Anti-fracturative drugs contain various molecular targets and mechanisms of action, and they are created for the remodelling of the bone, mineral metabolism or both.
First, through agonistic binding to oestrogen receptors alpha and beta, selective oestrogen receptor modulators copy oestrogen and prevent hormonal side-effects on the uterus lining and breast glands. Clinical trials showed that raloxifene increased bone density by 1.8% in the lumbar spine and 2.1% in the hip, while bazedoxifene and lasofoxifene also increased bone mass at the femur and lumbar spine in postmenopausal women.
Second, bisphosphonates also lessen fragility structures by 40-70% in both postmenopausal women and men with osteoporosis due to its strong chemical link for bone hydroxyapatite and inhibitory on the osteoclast. Side-effects for the treatment have been found commonly in elders and people who spend a lot of their time on bed. It was found that two of the gravest adverse reactions included bisphosphonate-related osteonecrosis of the jaw and atypical subtrochanteric femoral fractures.
Third, parathyroid hormone as well as its derived recombinant peptide teriparatide are also able to balance calcium and phosphorus by acting on the bone and kidneys, and this results in the increase of bone mass.
Fourth, calcitonin reduces bone resorption by specific binding to calcitonin receptor on the surface of the osteoclast, and after administration, it was found that calcitonin had increased the bone mass and has reduced the risk of spine fracture by 33%, but has been associated with higher risk of cancer.
Fifth, strontium ranelate stimulates pre-osteoblast differentiation and osteoblast synthesis of bone matrix proteins, preventing bone absorption and allowing bone formation in postmenopausal women with osteoporosis, but increasing the risk of having side-effects related to the heart.
Lastly, anti-receptor activator of nuclear factor-kappB ligand, also known as anti-RANKL and denosumab, is now approved for osteoporosis treatment due to its ability to hinder its positive action on osteoclasts, but it is not yet used for prevention.
In conclusion, anti-fracturative drugs act differently within target cells and in effect, it causes some who are taking anti-fracturative drugs to respond poorly. This shows that genetic patient profile affects personal drug response. Currently, both non-response and adverse effects cannot be predicted before administering the drug. There is only one small negative study on pharmacogenetics of teriparatide, while there are no pharmacogenetics studies available on calcitonin, denosumab, and strontium ranelate therapies, or in the clinical trials of prospective anti-fracturative novel molecules. Pharmacogenetic studies about the positive association between genetic profile and anti-fracturative drugs response have not yet been replicated; thus, their validity and application in practice are yet to be confirmed. In addition, studies show that ethnic difference, the small population tested, use of various drugs including concomitant drugs, doses, or both, retrospective clinical trials use, no supplementation with calcium or vitamin D, or both, and countless factors affecting lifestyle, environmental factors, and dietary habits of the tested population may be the reasons behind the negative associations and contradictory results.
Recommendations include properly deciding on the design of clinical trials, monitoring patients' conformance to the given medication, evaluating adverse reactions through long-term check ups, duplicating positive results in different ethnic groups and bigger populations, researching pharmacogenetics side-effects of proposed anti-fracturative drugs, using different techniques specifically GWA and NGS, validating researches in both animal and human models and assessing the role of epigenetic factors and of the possible connection of genes and exogenous factors.
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