Osteoporosis: Diagnosis and Managements _ _____________________________________________________
There is no good data regarding the use of calcitonin in reducing hip fractures or preventing any fractures in patients without pre-existing fracture [35; 49]. Calcitonin may have a role in patients with acute vertebral fractures due to a possible analgesic effect and its decreased risk of gastrointestinal upset and venous thromboembolism associated with other agents [120]. It has been shown to preserve bone mass by about 3% in the first year of glucocorticoid therapy [121]. Adverse effects from the injectable form include nausea, back pain, frequent urination, arthralgias, and rash. The intranasal form has fewer side effects, which are primarily localized and include rhinitis and, rarely, epistaxis [20; 73; 122]. Bone-Formation Agents The original FDA-approved medications for osteoporosis were antiresorptives. Newer medications act instead to enhance bone formation by increasing the number and action of osteoblasts. The human PTH agents teriparatide and abaloparatide have been approved for use in the treatment of osteoporosis in patients with very high fracture risk [72; 73]. Parathyroid Hormone PTH acts normally to increase bone resorption in response to low serum calcium levels; however, in intermittent doses, it has been shown to have a favorable impact on bone mineral density [23]. Teriparatide is a portion of human PTH, classified as PTH (1–34) and, as noted, has been approved by the FDA for the treatment of osteoporosis in postmenopausal women at high risk for a fracture. It also has been approved to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for a fracture [20; 23; 36; 73; 123]. The FDA has approved an expanded indication for teriparatide for treatment of osteoporosis associated with sustained systemic glucocorticoid therapy (≥5 mg/day of prednisone). For this indication, teriparatide is available as 20 mcg once daily subcutaneous injection [20; 73]. Biosimilar preparations are now available, as the patent expired in 2019 [20]. Teriparatide stimulates new bone formation by increasing the number and action of osteoblasts. Specifically, it increases the number of osteoblasts through the induction of osteoprogenitor cell differentiation in the bone marrow. In addition, it prevents osteoblast apoptosis. It is offered as a daily injection and recommended for use in patients with severe osteoporosis, especially those who have failed other treatments [73]. In a pivotal trial of more than 1,500 postmenopausal women, there was a 65% reduction in new vertebral fractures compared with placebo over 19 months of treatment. New nonvertebral fractures were reduced by 56% [20]. Ninety-six percent of women had an increase in BMD. Side effects included nausea, leg cramps, and dizziness [124]. Treatment with teriparatide is not recommended for more than 18 months to 2 years, nor should it be prescribed to patients with pre-existing hypercalcemia [73; 123]. Before it may be prescribed, it is necessary to obtain baseline measurements of calcium, uric acid, current PTH level, creatinine, and 25
hydroxyvitamin D to be certain that hypercalcemia is not present. These values should be re-examined periodically [73; 123]. Of note, there was an increase in the incidence of osteosarcoma in rats that was dependent on dose and duration of treatment, although no cases of osteosarcoma were reported in patients during the clinical trials. Teriparatide should not be prescribed for patients at increased risk for osteosarcoma, patients with Paget disease or unexplained elevations of alkaline phosphatase, or those who have undergone prior skeletal radiation therapy [20; 73; 123]. Because prior use of the bisphosphonates may interfere with the action of PTH (1–34), it has been recommended that teriparatide only be administered to bisphosphonate-naïve patients [73; 123]. Side effects include leg cramps, dizziness, nausea, cramps, pharyngitis, asthenia, and headache [20; 73]. Like teriparatide, abaloparatide is a portion of human PTH, classified as PTH (1–34) and, as noted, has been approved by the FDA for the treatment of osteoporosis in postmenopausal women at high risk for a fracture [20; 72; 73]. Abaloparatide stimulates new bone formation by increasing the number and action of osteoblasts by acting as an agonist at the PTH1 receptor [73; 125; 126]. It is offered as a subcutaneous 80-mg daily injection [73]. As with teriparatide, abaloparatide therapy is not recommended for more than two years and is not recommended for patients with pre-existing hypercalcemia or an underlying hypercalcemic disorder (e.g., primary hyperparathyroidism) [73]. Before it is prescribed, it is necessary to obtain baseline measurements of calcium, uric acid, current PTH level, creatinine, and 25 hydroxyvitamin D to be certain that hypercalcemia is not present. These values should be re-examined periodically [73]. Abaloparatide has been shown to reduce the risk of new vertebral and nonvertebral fractures, major osteoporotic fractures, and clinical fractures, with a significant improvement in BMD at femoral neck, total hip, and lumbar spine [127; 128]. Romosozumab-aqqg Romosozumab-aqqg is a monoclonal antibody that blocks the effects of the protein sclerostin and works mainly by increasing new bone formation [20; 74]. It is approved for the treatment of osteoporosis in postmenopausal women with a history of osteoporotic fracture, with multiple risk factors for fracture, or those who have failed or are intolerant to other osteoporosis therapies [20]. The result of two clinical trials involving more than 11,000 women with postmenopausal osteoporosis, one year of treatment with romosozumab-aqqg lowered the risk of vertebral fracture by 73% compared with placebo [74]. One dose consists of two injections, one immediately following the other, given once a month. The bone forming effect wanes after 12 doses, so more than 12 doses should not be used.
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