Summary of the technology
Up to date there is not any technology for detecting the risk to suffer atypical fractures related to long-term treatment with bone remodelling inhibitors. The invention will be of usefulness for individualize treatments in patients treated with bone remodelling inhibitors by detecting the individual risk of suffering atypical fractures.
The invention is planned to be included into an in-vitro diagnostic tool for the atypical fracture, which will be included into standard disease management protocols and therefore used routinely by physicians prior to and after the prescription of bone remodelling drugs and further osteoporosis drugs. Osteoporosis is a progressive bone disease with a characteristic decrease in bone mass and density which can lead to an increased risk of fracture. There are two types of osteoporosis: •Type 1: most common in women after menopause, named postmenopausal osteoporosis •Type 2: Senile osteoporosis, occurs mostly after age of 75 years and has equally effect in women and in men Based on the WHO diagnostic criteria, approximately 22 million women and 5.5 million men aged between 50 and 84 years had osteoporosis in the European Union (EU) in 2010, whilst osteoporosis can be found in the list of 10 most important diseases named by the WHO. Due to changes in population demography, the number of men and women with osteoporosis might rise from 27.5 million in 2010 to 33.9 million in 2025, corresponding to an increase of 23%. The number of new fractures in the EU in 2010 was estimated at 3,5 million cases, in between these approximately 620.000 hip fractures, 520.000 vertebral fractures, 560.000 forearm fractures and 1.800.000 fractures of i.e. pelvis, rib, humerus, tibia, fibula, clavicle, scapula, sternum, and other femoral fractures. Two thirds of all fractures occurred in women. In 2010, the number of deaths causally related to fractures was estimated at 43.000. The corresponding cost of osteoporosis in the EU, also in 2010 figures, including pharmacological intervention, was estimated at €37 billion out of which costs of treating fractures represented 66%, pharmacological prevention 5% and long term fracture care 29%. The total health burden was estimated at 1 180 000 lost Quality Adjusted Life Years (QALY) for the EU. The total cost in the EU might rise from €98 billion in 2010 to €120 billion Euro in 2025. The use of osteoporosis drugs has increased considerably. Approved pharmacological interventions (bisphosphonates, strontium ranelate, raloxifene, denosumab and parathyroid hormone peptides) are widely available but their use is restricted by reimbursement policies. Alendronate (a bisphosphonate) is the most commonly prescribed agent, accounting for approximately a quarter of the total value of sales. The potential users/partners are pharmaceutical companies, excluding pure generic companies (lacking development resources, relevant lobbying and sales channel to the policy makers and practitioner) selling drugs in the indication osteoporosis
Description of the technology
Bisphosphonates are currently considered first choice treatment of osteoporosis. However, long-term bisphosphonate therapy increases the risk for suffering atypical fractures. These fractures are located in the subtrochanteric region or femoral shaft and do not meet the classic profile of osteoporotic fragility fractures. The present invention relates to a method for detecting the genetically transmitted risk of atypical fractures in patients suffering bone diseases treated with inhibitors of bone remodelling or that are eligible for treatment with such drugs
The invention is planned to be used in an in-vitro diagnostic tool for the determination of the risk of the stated atypical fractures in patients treated, or to be treated, with bone remodelling inhibitors. The invention makes use of the mutation c.562G>T of the gene GGPS1 as a biomarker for developing an individual in-vitro diagnostic or, more likely, as a biomarker to be used in a development of multiple biomarkers into a combined kit for an in-vitro diagnostic.
Main advantages of its use
- The antifracture efficacy of bone remodelling inhibitors (bisphosphonates, denosumab) has been proven in clinical trials. However, with more extensive and prolonged clinical use of these drugs, the occurrence of rare, but serious, adverse events as the atypical fractures have been reported. Increasingly over recent years, the diagnostic process has become more strongly driven by the need to pre-select patients based on drug labels and licenses. Therefore, most physicians are already used to the role of diagnostic tests to clarify and support their clinical decision-making. The demand for diagnostics detecting genomic or gene expression markers to accompany therapies is growing. The sharpening focus on biomarker testing by the regulatory sector is highlighted by the growing number of drugs with this information in their labels. Pharmacogenomic information is currently contained in approximately 10% of labels for drugs approved by the FDA and, interestingly, the FDA has recently started publishing a table of genomic biomarkers that it considers valid in guiding the clinical use of approved drugs. Being able to present reliable biomarkers for reducing adverse effects of prolonged clinical use of bone remodelling inhibitors, might induce regulatory pressure towards a standard diagnostic use in osteoporosis patients.
- The invention is planned to be included into an in-vitro diagnostic tool for the atypical fracture, which will be included into standard disease management protocols and therefore used routinely by physicians prior to and after the prescription of bone remodelling drugs and further osteoporosis drugs