What are the precautions for osteoporosis treatment drugs?🦴🦴🦴

Osteoporosis is a systemic metabolic bone disease in which bone mass and
bone density decrease due to different reasons. Osteoporosis is common in postmenopausal women and older men. It is a very common bone disease. It is characterized by increased bone fragility and increased susceptibility to fractures. Osteoporosis can be divided into primary osteoporosis and secondary osteoporosis according to different etiologies.

What is primary osteoporosis?

Primary osteoporosis includes postmenopausal osteoporosis (type I), senile osteoporosis (type II) and idiopathic osteoporosis. Postmenopausal osteoporosis generally occurs within 5 to 10 years after menopause in women. Senile osteoporosis usually occurs after age 70. Idiopathic osteoporosis occurs mainly in adolescents.

What is secondary osteoporosis?

Secondary osteoporosis refers to osteoporosis caused by drugs (such as proton pump inhibitors, antiviral drugs, glucocorticoids, etc.) and/or diseases affecting bone metabolism and other causes.

What medicines are available for the treatment of osteoporosis?

Osteoporosis treatment drugs mainly include basic supplements for bone health, bone resorption inhibitors, bone formation promoters, active vitamin D and its analogs.

Basic supplements for bone health.

The basic supplements for osteoporosis prevention and treatment are calcium and vitamin D.

Calcium: 

• Commonly used are calcium citrate and calcium carbonate. Although calcium citrate has a lower calcium content, its better water solubility can reduce the occurrence of kidney stones. It is suitable for patients who are at risk of kidney stones or who are achlorhydric. Calcium carbonate has a higher calcium content. It is easily soluble in gastric acid and has a high absorption rate by the human body. 
• Epigastric discomfort and constipation are their common adverse effects. Calcium citrate has relatively few gastrointestinal adverse effects. Calcium should be avoided in patients with hypercalcemia and hypercalciuria. High-dose calcium may increase the risk of cardiovascular disease and kidney stones. Fluoroquinolones will complex with calcium ions in calcium. This hinders the absorption of the drug and can easily lead to the failure of anti-infective therapy.

Vitamin D:

• The combination of vitamin D and calcium reduces the risk of osteoporotic fractures. In addition, the efficacy of other anti-osteoporosis drugs can be enhanced by adequate vitamin D supplementation. Elderly osteoporosis patients who are obviously deficient in vitamin D should use vitamin D supplementation, and at the same time, they can use active vitamin D to treat osteoporosis under the guidance of doctors.
• Urinary and serum calcium concentrations should be monitored regularly when taking vitamin D to prevent hypercalcemia and hyperphosphatemia. In addition, taking active vitamin D to correct basal vitamin D deficiency is generally not recommended. Supplemental therapy with larger doses of vitamin D is not recommended for multiple doses within a year.

Bone resorption inhibitors.

Such drugs mainly include bisphosphonates, calcitonins and selective estrogen receptor modulators.

Bisphosphonates:

• Broad-spectrum anti-fracture drugs such as alendronate, risedronate, and zoledronic acid are the preferred drugs. Oral bisphosphonates such as alendronate and risedronate should be the first choice for people with low bone mineral density but no history of fractures and people with low or moderate fracture risk. Injectable forms such as zoledronic acid may be considered in elderly patients with multiple vertebral or hip fractures, as well as in people with high fracture risk, very low bone mineral density, contraindications, or oral intolerance. Lumbar spine and hip bone mineral density in people with osteoporosis can be improved with zoledronic acid. It reduces the risk of vertebral, nonvertebral and hip fractures.
• Their adverse reactions include renal toxicity, osteonecrosis of the jaw, atypical femoral fractures, transient flu-like symptoms, and gastrointestinal reactions. Bisphosphonates should be used with caution in patients with reflux esophagitis, active gastric and duodenal ulcers, and functional esophageal dysfunction. Bisphosphonates are not recommended for patients with severe oral disease or in need of dental surgery. They should also be contraindicated in patients with creatinine clearance <35ml/min. After 3 years of intravenous bisphosphonate use or 5 years of oral bisphosphonates, patients should be reassessed to determine whether continued use of the drug is required.

Calcitonin drugs:

• The biological activity of osteoclasts can be inhibited by calcitonin drugs. They reduce the number of osteoclasts and the loss of bone mass. They also relieve bone pain and increase bone mass. In particular, it can significantly relieve bone pain caused by osteoporosis and fractures.
• Their main adverse reactions are nausea, facial flushing, etc., and occasionally allergic phenomena occur. Because calcitonins have the potential to increase the risk of developing tumors, they should generally not be used continuously for more than 3 months.

Selective estrogen receptor modulators:

• A commonly used selective estrogen receptor modulator is raloxifene. It is indicated for the treatment of postmenopausal osteoporosis and for reducing the risk of vertebral fractures.
• Raloxifene may cause pulmonary embolism and deep vein thrombosis. Therefore, it is contraindicated in those with a history of venous thrombosis and those with thrombophilia (such as those who are sedentary or bedridden for a long time). In addition, the risk of thromboembolism in patients should be strictly assessed before administration.

Bone formation promoter.

Parathyroid hormone analog:

• Teriparatide is a parathyroid hormone analog. It stimulates osteoblast activity by intermittently administering small doses. It increases bone density and promotes bone formation. It also reduces the risk of non-vertebral and vertebral fractures.
• Dizziness, headache, nausea and limb pain are its common adverse effects. Because of the risk of osteosarcoma formation after two years of teriparatide use, it should not be given for more than two years. Patients should also be treated with anti-resorptive drugs sequentially after drug discontinuation to maintain or increase the patient's bone density. This continuously reduces the risk of fractures.

Active vitamin D and its analogs.

These drugs are suitable for patients with impaired renal function, reduction or deficiency of 1-alpha-hydroxylase, and the elderly.

Alpha-calcidol, calcitriol:

• Although α-calcidol does not need to be activated by renal metabolism, it needs to be activated by 25-hydroxylase in the liver to have biological activity. Calcitriol itself has biological activity. In addition, the effect of calcitriol to increase blood calcium will be stronger than that of α-calcidol. However, it has a shorter half-life than alpha-calcidol and loses its efficacy about 2 to 3 days after stopping the drug. After you stop taking alpha-calcidol, it takes about 1 week for it to stop working.
• Active vitamin D and its analogs have a significantly higher risk of hypercalciuria relative to vitamin D. The risk of hypercalcemia increases with higher doses, especially when combined with calcium supplements. Therefore, patients' urinary calcium and serum calcium should be monitored during treatment, especially when combined with calcium supplements. Active vitamin D and its analogs are used with caution in patients with kidney stones and are contraindicated in patients with hypercalcemia. It also increases the risk of hypercalcemia when combined with thiazide diuretics. It may cause hypermagnesemia when used with magnesium-containing drugs, especially in patients with chronic renal failure. It can induce cardiac arrhythmias when combined with digitalis.