The importance of osteoporosis causing bone fractures, the risk factors, diagnostics, osteoporosis measurements: bone mineral density and fracture risk were discussed in our previous blog. Vitamin D and calcium supplementation, physical activity and diet for preventing the serious fracture consequence were also analysed.
Vitamin D and calcium supplementations are always necessary, particularly in the case of postmenopausal women and men above the age of 55, when they have many risk factors of osteoporosis, or they have a high fracture risk (FRAX MAI > 20%, FRAX HIP > 3%) or osteoporosis diagnosed by bone mineral density (T-score < -2.5), or an osteoporotic fracture has already happened.
If, in spite of the supplementary therapy, osteoporosis further progresses or an osteoporotic fracture occurs, antiporotic therapy is required. The purpose of the antiporotic treatment is to prevent bone fracture (primary prevention) as well as to prevent further fractures (secondary prevention) caused by OP.
In the case of primary prevention an osteoporotic fracture has not yet developed, but BMD and FRAX have reached the critical threshold (T-score < -2.5, FRAX MAI > 20% FRAX HIP > 3%). In the case of secondary prevention an osteoporotic fracture has already developed, and either BMD or FRAX has reached the threshold.
It is obvious, that in the case of secondary prevention BMD measurement is not necessarily required to initiate antiporotic treatment. Nevertheless, BMD must be measured within 4 months.
First line antiporotic drugs inhibit bone resorption. In Hungary the first antiresorptive drug, the bisphosphonate (BP) named Fosamax was introduced in 2000. To this day the BPs remain the drug of choice. BPs bind firmly to the bone cells, their antiresorptive effect is significant and lasts for appr. 4-5 years after medication.
For BP therapy patient compliance in the long term is vital. The inconveniences of BP treatment are: BP tablets must be taken on an empty stomach, with a glass of water, in an upright position, lying down and drinking/eating are prohibited for 30 minutes after intake. These requirements are needed in order to prevent gastrointestinal side effects.
During the application of BP treatment, an extremely rare but serious complication might occur, which is osteonecrosis of the jaw (ONJ). Dental consultation is therefore obligatory before starting BPs. In the development of ONJ poor oral hygiene (ie. smoking) is the most important factor. During BP therapy supplementary calcium and vitamin D are especially crucial to preserve balance of bone metabolism.
It is the decision of the patient’s doctor as to which BP product to use. If no contraindication exists BPs are first recommended orally. There are many BP products nowadays, the main molecules are alendronate, risedronate and ibandronate.
The patient’s oral therapy has to be switched to parenteral treatment, if patient compliance is inappropriate, or drug intolerance develops, or oral BP is originally contraindicated. The best known parenteral BPs are quarterly injections of ibandronate and annual injection of zolandronate.
Biological therapies have also appeared in the field of osteoporosis (2010). The monoclonal antibody, named denosumab (Prolia/Xgeva) specifically binds to RANKL, a specific cytokine involved in bone metabolism, thus significantly reducing bone resorption, increasing bone density and decreasing the risk of vertebral and non-vertebral osteoporotic fractures.
Denosumab is an alternative option in the secondary prevention of osteoporotic fractures, but it can also be used in primary prevention if previous medications are contraindicated, if there is intolerance, if bone mineral density (BMD) improvement is less than 5% after 12 months of treatment, or a new osteoporotic fracture occurs.
Before administering denosumab, serum calcium levels must be checked, and it should only be given if calcium levels are normal.
Dental control is also needed before denosumab therapy, and should be carried out before treatment introduction. If a dental treament is unexpectedly needed during denosumab therapy, the best period is between the 6th and 8th month after injection.
There is no time limit for the length of denosumab therapy, but after completion some kind of a bisphosphonate must be prescribed. Denosumab effect lasts for 8 months after injection, whereas that of bisphosphonates for 4-5 years. After finishing bisphosphonates a drug holiday is advised to observe whether no relapse occurs.
The next step in osteoporotic treatment, which has become widespread in recent years, is teriparatide (Forsteo, biosimilars Terrosa, Movymia etc.), a human parathyroid hormone analogue produced by DNA technology, which, instead of reducing bone resorption, mainly promotes bone formation.
Teriparatide is more effective in preserving bone density and treating osteoporotic fractures than bone resorption inhibitors. It has been proven that systemic daily doses of parathyroid hormone promoted coordinated bone remodeling, shifting the process towards bone formation. Numerous animal experiments and human clinical trials have confirmed that teriparatide accelerated bone healing and improved the mechanical properties of the bone.
Teriparatide can be used as an alternative treatment in the secondary prevention of fragility fractures if previous medications are contraindicated, if there is intolerance, if bone density improvement is less than 5% after 12 months of treatment, or a new fracture occurs. It can also be used as the drug of choice in secondary prevention if a postmenopausal woman or a man over 55 years old has at least one fragility fracture and a T-score < - 4.0 or a FRAX MAI > 20% / FRAX HIP > 3%, or if they have suffered at least two fragility fractures and a T-score < -3.0 or FRAX MAI > 20% / HIP > 3%.
Teriparatide can be administered for 18 (maximum 24) months. After prolonged administration, some reports have indicated the development of bone tumors and its use is prohibited in Paget's disease. Parathyroid hormone therapy should always be continued with bone resorptive agents. Serum calcium levels must be strictly monitored during its administration.
There are increasing data in the international literature suggesting that teriparatide is effective in treating drug-induced osteonecrosis of the jaw (ONJ) otherwise resistant to traditional treatments.
There are internationally accepted and standardized algorythm for the treatment of OP.