10/09/2024
Osteoporosis is a systemic bone metabolism disorder mainly characterized by low bone mineral content, destruction of bone structure, reduction of bone strength and susceptibility to fracture. According to statistics, the common clinical osteoporosis in 8% to 15% of people is not due to calcium deficiency, vitamin D or disease, but by the drugs lead to mineral metabolism disorders in the body, clinically also known as drug-induced osteoporosis. Today we take a look at the drugs that can cause osteoporosis.
Glucocorticoid
Glucocorticosteroids are the most common drugs that cause osteoporosis, mainly related to glucocorticosteroids promote protein breakdown, inhibit its synthesis and increase calcium and phosphorus excretion. It is most common in children, menopausal women and the elderly, and in severe cases, spontaneous fractures can occur.
Anticoagulants
Warfarin can also cause osteoporosis, which may be related to its inhibition of calcitonin deposition and promotion of bone resorption. It often occurs in the distal radius, spine and hip bones, but also in the ribs.
Heparin-induced osteoporosis often occurs in the spine and ribs. The mechanism of action may be related to its ability to increase collagen dissolution, accelerate bone resorption due to hyperthyroidism, and inhibit bone formation. The risk of osteoporosis from low molecular heparin is lower than that from regular heparin.
Thyroid hormones
Thyroid hormone promotes protein synthesis and growth and development of bones and the central nervous system. It is mainly used in the treatment of hypothyroidism and simple goiter. It can cause osteoporosis by inhibiting osteoblast activity, promoting osteoclast formation and secretion, and affecting calcium and phosphorus metabolism. When thyroid hormone replacement therapy is used, bone conversion is also related to the level of thyrotropic hormone, and those with higher levels of thyrotropic hormone have a higher tendency to develop osteoporosis.
Proton pump inhibitors
The U.S. Food and Drug Administration (FDA) issued a warning on May 25, 2010 that proton pump inhibitors (PPIs) may increase the risk of hip, wrist, and spine fractures based on a review of seven epidemiologic studies. Most of the observed risk was in patients over 50 years of age and in patients taking higher doses of PPIs or with a history of use longer than 1 year.
The mechanism is not well understood and may be related to the inhibition of gastric acid secretion by PPIs, which leads to impaired intestinal calcium absorption, feedback-induced increases in the secretion of parathyroid hormone and 1,25-dihydroxyvitamin D3, as well as the promotion of osteolysis and increased bone resorption.
Antiepileptic drugs
Long-term use of antiepileptic drugs such as phenytoin sodium and phenobarbital can cause osteoporosis. These drugs can cause osteoporosis by promoting the degradation of vitamin D, reducing the absorption of calcium ions, decreasing the body's response to parathyroid hormone, and causing vitamin K and calcitonin deficiency.
Aromatase inhibitors
Postmenopausal breast cancer patients have a further acceleration of bone loss and an increased risk of fracture compared to healthy women of the same age, resulting in increased disability and mortality. The use of aromatase inhibitors (AIs) (anastrozole, letrozole, etc.) is a risk factor for bone loss in postmenopausal breast cancer patients. Estrogen promotes osteoclast apoptosis, inhibits bone resorption and promotes osteoblast differentiation, and AIs can reduce estrogen levels, thereby accelerating bone loss and increasing fracture risk in patients.
Protease inhibitors
HIV-1 may affect bone metabolism by infecting osteoblasts. Low body mass, vitamin D deficiency, and hypogonadism in HIV-1-infected individuals also affect the skeletal system. Studies have found that the incidence of osteoporosis and bone loss is much higher in HIV-1-infected individuals than in the general population.
A meta-analysis showed that the use of highly active combination antiretroviral therapy (HAART), especially protease inhibitors, was a risk factor for reduced bone mineral density in HIV-1-infected patients, with the risk of osteoporosis in those receiving HAART being three times higher than that of the control group.
In vitro studies have shown that ritonavir affects bone metabolism either by affecting osteoclast differentiation through the classical Wnt signaling pathway or by predisposing osteoclasts to differentiation mediated by the non-classical Wnt signaling pathway. Protease inhibitors may also indirectly affect bone metabolism by inhibiting hydroxylase activity and preventing the efficient conversion of 25-(OH)D3 to 1,25-(OH)2D3.
Osteoporosis Drugs
Yes, osteoporosis drugs may also cause osteoporosis and fractures. Bisphosphonates are used in menopausal women to prevent or slow down bone loss to reduce the risk of osteoporotic fractures.
The FDA issued a warning on October 13, 2010 that bisphosphonate osteoporosis medications taken for more than five years may increase the risk of subrotary and diaphyseal femur fractures. Such drugs include zoledronate, pamiphosphate disodium, risedronate, ibandronate, and alendronate. Experts believe this may be due to the fact that the process of the bone reorganizing itself is affected, which prevents it from repairing itself.
Denosumab is a human monoclonal antibody, a bone resorption inhibitor with a unique mechanism of action that inhibits osteoclast activation and increases spine, hip, and radius bone density and strength, reducing the risk of fracture. in november 2012, health canada warned that denosumab may be associated with an unusual risk of femur fracture in a small number of patients. the announcement stated that treatment with denosumab may be associated with a risk of femur fracture in a small number of patients. The announcement said patients treated with denosumab should immediately inform their doctor if they experience dull or unusual pain in the thigh, hip, or groin.
Thiazolidinediones
Thiazolidinediones glucose-lowering drugs such as rosiglitazone and pioglitazone are insulin sensitizers used primarily to treat insulin-resistant type 2 diabetes.In 2006, the New England Journal reported that rosiglitazone increased the risk of osteoporotic fractures in patients.
Since then, several studies have shown that this class of drugs increases bone loss and decreases bone density and bone mass. Osteoporosis caused by it often presents with generalized skeletal involvement, commonly in the upper extremities, involving the humerus and hands. The mechanism of action may be related to its promotion of osteoclast differentiation and bone resorption, inhibition of osteoblast differentiation and bone formation, and may also be related to its effect on the aromatase system, reduce estrogen synthesis, increase bone resorption, agonist nuclear transcription factor peroxisome proliferator-activated receptor γ (PPAR-γ) and so on.
Tumor chemotherapy drugs
Many chemotherapeutic drugs can affect the skeletal system, such as methotrexate causes osteoporosis by decreasing osteoblast activity and increasing osteoclastogenesis, and long-term application of large doses even leads to methotrexate bone disease (bone pain, osteoporosis, compression fracture); cyclophosphamide can cause osteoclast damage resulting in osteogenesis and affecting bone metabolism; adriamycin inhibits osteoclasts to make the thickness of the bone marrow and bone cortex decrease. The thickness of bone cortex and bone marrow decreases by inhibiting osteoblasts.
In addition, diuretics, isoniazid, lithium, calcium-modulated phosphatase inhibitors, aluminum-containing antacids, and gonadotropin-releasing hormone analogs can cause osteoporosis and increase the risk of fracture. Clinical pharmacists recommend taking the above drugs should pay attention to monitoring urinary calcium, blood 1,25-(OH)2D3, mineral levels, bone density and other indicators, or under the guidance of a doctor or pharmacist to take calcium, vitamin D, calcitonin, estrogen and other drugs to prevent osteoporosis.
