2023-07-05 02:07:00
1. Osteoporosis, what should be the criteria for treatment and follow-up? Professor Sehwa Kim (Catholic Kwandong University)
2. Female hormones and SERM preparations When and to whom should they be used first? Professor Lee Dong-ok (National Cancer Center)
3. Precautions for bisphosphonate drug withdrawal and denosumab discontinuation Prof. Choi Han-seok (Dongguk University College of Medicine)
4. Bone formation promoters (parathyroid hormone and romosozumab) When and whom should be considered first?
Kang Kyung-joong Professor (Kyung Hee University)
4. Bone formation promoters (parathyroid hormone and romosozumab) When and whom to consider first? – Professor Kang Kyung-joong
Introduction
Osteoporosis is a disease of the elderly and its prevalence is increasing. 25% of postmenopausal women and 40% of the total population over the age of 80 experience vertebral compression fractures, and accordingly, the pharmaceutical market related to osteoporosis is developing rapidly compared to other diseases.
It is reported that the mortality rate following hip fracture is 20% within 1 year, and the mortality rate following vertebral fracture is also close to 14.6% within 1 year and 20% within 2 years. If you have a femur fracture or a vertebral fracture, it can be seen as a serious osteoporosis, and in such cases, active treatment is essential. Representative osteoporosis treatment drugs that have been traditionally used include female hormone therapy, selective estrogen receptor modulator (SERM), bisphosphonate, calcium, and vitamin D. Drugs that have been used with interest relatively recently include denosumab and parathyroid hormone preparations. and romosozumab. Among these, we will look at parathyroid hormone preparations and romosozumab, which are bone formation promoters.
Parathyroid hormone (PTH)
Teriparatide, one of the parathyroid hormone preparations, is a recombinant human parathyroid hormone (rhPTH), and as a bone formation promoter, it inhibits the apoptosis of osteoblasts and is involved in the formation of osteoblasts through osteoblast production and the production of sclerostin. impede It has been approved by the US FDA in 2002 and has been considered the only drug that increases the production of bone tissue among currently used agents. Its clinical use is limited to within 24 months.
Teriparatide has an anti-fracture effect, and it is generally known that teriparatide improves fracture union and function in patients with osteoporosis. Clinical studies have reported that using teriparatide following spinal fusion in postmenopausal osteoporotic women increases the rate of bone union and reduces hardware loosening.
In addition, a study was conducted on the simultaneous use of teriparatide and denosumab in postmenopausal women with osteoporosis. According to a study (2016, The Journal of Clinical Endocrinology & Metabolism), using both drugs together is more According to another combination treatment study (2015, Lancet), simultaneous use of teriparatide and denosumab improves bone density more than using either agent alone. (BMD) has been reported to increase more.
In 2006, a report was published in the World Journal of Osteoporosis that the use of teriparatide significantly reduced pain in patients with simple lumbar pain even in patients without fractures. Since then, several other studies have reported that it helps control pain, including lumbar pain, and in another study, it is known that it is effective in reducing pain significantly compared to bisphosphonate preparations even in patients with fractures. In 2020, an interesting study through animal experiments was published on the pain control of teriparatide. In this study, teriparatide acts on nerve cells as well as bone cells to show a hyperalgesic effect. Pain control was explained.
Another study (2006, Osteoporosis international) reported that the probability of back and back pain following 30 months when Teriparatide was discontinued was relatively lower than when bisphosphonates were discontinued.
Several studies have shown that Teriparatide avoids nonunion at the site of osteoporotic fractures, restores function, and shortens the recovery period. In addition, in a study on whether progressing kyphosis and collapse in vertebral compression fractures can be prevented, it has been reported to be significantly more effective than the bisphosphonate group. However, there is also a result that it is not effective for fracture recovery and pain control, especially in areas other than the spine, in young patients without osteoporosis, so more research is still needed.
For atypical femoral fractures, a complication associated with long-term use of bisphosphonates, teriparatide may be used as a first-line treatment. It has also been reported to be highly effective in treating medication-related osteonecrosis of the jaw (MRONJ) by reducing bone defects. However, the incidence of these side effects is low, so there are not many research data, and additional research is also needed.
On the other hand, it has been reported that switching from teriparatide to denosumab increases bone density in postmenopausal women with osteoporosis, whereas switching from denosumab to teriparatide causes gradual or temporary bone loss.
As a side effect, hypercalcemia may occur, so it is necessary to measure blood calcium level following administration. In case of patients with high blood calcium level, it should be used with caution. In theory, there is a possibility of cancer such as osteosarcoma. Forbid the use.
Abaloparatide, another parathyroid hormone drug, is a drug approved by the FDA in 2017. It is a parathyroid hormone-related protein analog that selectively activates the signal transduction system of the type 1 receptor of parathyroid hormone to act as a bone formation promoter. will use
It promotes bone formation and resorption in postmenopausal women with osteoporosis, and a study was also published in the JAMA journal in 2016. According to the results, daily subcutaneously administered abaloparatide increased BMD more significantly than teriparatide, and this BMD increase was more pronounced in cortical bone. In addition, it causes less hypercalcemia than when using teriparatide, and no serious side effects have been reported following administration. Side effects that may occur are relatively mild, such as nausea, dizziness, headache, and palpitations. Although it is not clinically used in Korea yet, it is expected to have similar effects to Teriparatide.
Romosozumab
Romosozumab is a humanized monoclonal antibody to sclerostin. Sclerostin is a glycoprotein produced by osteoclasts that blocks Wnt signaling that promotes bone formation. Therefore, romosozumab shows the dual effect of increasing bone formation and decreasing bone resorption.
According to studies, romosuzumab administered subcutaneously in a 1-month cycle is known to produce an increase in bone density and an increase in bone formation markers and a continuous decrease in bone resorption markers from 6 to 9 months following the first administration. In addition, it has been reported that it can reduce the risk of fractures in other parts including the spine in postmenopausal women with osteoporosis.
Although it has not been approved by the FDA for a long time and more research is needed, it is currently the most popular drug in the market as an osteoporosis drug, and is known to greatly increase bone density and rapidly reduce the risk of fracture. A double-blind study comparing blood P1NP (bone formation marker) and CTX levels (bone resorption marker) with the placebo effect following 12 months showed significantly improved results. Compared to alendronate, a bone resorption inhibitor, romosozumab reduced the incidence of vertebral fractures by 37% and nonvertebral fractures by 26% within 12 months. In addition, in a research paper comparing teriparatide and romosozumab, which are existing bone forming agents, following using oral bisphosphonate preparations, when the results were compared for 12 months, it was confirmed that the BMD values of the hip joint, femoral neck, and lumbar spine improved when romosozumab was used. might
As a side effect of Romosozumab, there is a risk of cardiovascular disease, which is known to be related to vascular problems, which are the original effects of Wnt signaling itself. Therefore, treatment is contraindicated in patients with cerebrovascular disease or cardiovascular disease within the past year. Need attention. In addition, since hypocalcemia may occur, it is necessary to measure the calcium concentration. It is known that the bone forming effect appears only for one year, so use is permitted for up to one year.
conclusion
When used following spinal fusion, teriparatide can increase the rate of bone union and reduce instrument glass, so it is recommended to use teriparatide in such patients. Changing medications will help improve bone density.
Abaloparatide is similar to teriparatide, but it can be used in patients with high blood calcium levels or a history of cancer, which is a contraindication to teriparatide.
Romosozumab has been reported to reduce the risk of fractures in other parts including the spine in postmenopausal women with osteoporosis, so it can be of great help to this patient group. requires
So far, osteoporosis drugs have been reviewed among osteoporosis drugs. Since these drugs will be very useful treatment drugs, especially for patients with severe osteoporosis or a high risk of fracture, satisfactory results can be obtained if the precise characteristics and advantages of each drug are identified and treatment is carried out in consultation with a specialist. . ▣
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