Antiresorptive medications are a class of drugs used to manage various bone conditions by slowing down the natural process of bone breakdown. These medications help to maintain or even increase bone density, thereby reducing the risk of fractures and other skeletal complications.
Understanding Antiresorptive Medications
Bone is a dynamic tissue that constantly undergoes a process called remodeling, where old bone is removed and new bone is formed. Bone remodeling involves two cell types: osteoclasts, which break down old bone, and osteoblasts, which build new bone tissue. Antiresorptive medications primarily work by inhibiting the activity of osteoclasts, thus slowing down bone resorption. By reducing the rate at which bone is broken down, these medications help to rebalance the remodeling process, leading to increased bone density and strength.
How These Medications Work
Antiresorptive medications achieve their effects through different molecular mechanisms, primarily targeting osteoclasts. Bisphosphonates work by binding tightly to hydroxyapatite crystals, a component of bone. When osteoclasts resorb bone, they take up these bisphosphonate molecules. Nitrogen-containing bisphosphonates, such as alendronate, risedronate, and zoledronic acid, inhibit an enzyme called farnesyl pyrophosphate synthase within osteoclasts. This inhibition disrupts a pathway for osteoclast function and survival, leading to a decrease in bone breakdown and promoting osteoclast apoptosis.
Denosumab operates through a different mechanism as a monoclonal antibody. It targets and binds to a signaling molecule called RANK Ligand (RANKL), which promotes the formation, function, and survival of osteoclasts. By blocking RANKL from binding to its receptor (RANK) on osteoclasts and their precursors, denosumab directly inhibits osteoclast activity, reducing bone resorption and increasing bone mass and strength. Calcitonin is also an antiresorptive agent that directly inhibits osteoclast activity.
Conditions Treated by Antiresorptive Medications
Antiresorptive medications are prescribed for several conditions characterized by excessive bone loss or abnormal bone turnover. Osteoporosis is a primary indication. In osteoporosis, where bones become thin and weak, these medications prevent further bone loss, increase bone density, and reduce the risk of fractures.
Paget’s disease of bone is another condition treated with antiresorptive therapy, particularly bisphosphonates. This chronic metabolic bone disease involves abnormally high bone turnover. Bisphosphonates suppress this excessive bone resorption, helping to normalize bone remodeling and alleviate symptoms like bone pain.
Antiresorptive agents are also used in patients with bone metastases from cancer. When cancer spreads to the bones, it can lead to increased bone breakdown, pain, and fractures. Bisphosphonates and denosumab strengthen affected bones, reduce pain, and lower the risk of skeletal-related events, such as fractures and high blood calcium levels.
Important Considerations and Side Effects
While antiresorptive medications are beneficial for bone health, they can have side effects. Common side effects for oral bisphosphonates include gastrointestinal issues such as nausea, difficulty swallowing, heartburn, and irritation of the esophagus. Intravenous bisphosphonates may cause flu-like symptoms, fever, headache, and muscle or joint pain shortly after the first infusion, though these subside within two to three days with subsequent doses. Denosumab can lead to low calcium levels in the blood, so calcium and vitamin D supplementation are recommended. It may also increase the risk of infections, particularly skin infections.
Two rare but serious side effects associated with long-term use of antiresorptive medications, including bisphosphonates and denosumab, are osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). ONJ involves the breakdown and death of jawbone tissue, occurring after dental procedures like tooth extractions. The risk of ONJ is very low in patients taking these medications for osteoporosis, though it is higher in cancer patients receiving higher doses. Maintaining good oral hygiene and having a dental exam before starting treatment can help reduce this risk.
Atypical femoral fractures are unusual stress fractures that occur in the thigh bone with minimal or no trauma. These fractures are also rare, with the risk increasing with longer treatment duration, particularly beyond five years. Patients may experience a dull aching pain in the groin or thigh weeks or months before the fracture occurs, which should prompt medical evaluation. While these serious side effects are rare, patients should discuss any new or worsening symptoms with their healthcare provider.
Administering and Monitoring Treatment
Antiresorptive medications are administered through various routes and frequencies. Bisphosphonates are available as oral tablets, which can be taken daily, weekly, or monthly, or as intravenous injections, given every three months or once a year. Denosumab is administered as a subcutaneous injection every six months. The duration of treatment varies, with some bisphosphonates potentially allowing for a “drug holiday” after several years due to their persistence in bone. However, for drugs like denosumab, the effects diminish quickly upon discontinuation, necessitating continuous therapy or a switch to another medication.
Regular monitoring is part of antiresorptive treatment to assess its effectiveness and manage potential side effects. Bone mineral density (BMD) is measured using dual-energy X-ray absorptiometry (DEXA) scans, performed one to two years after starting treatment and less frequently thereafter. While changes in BMD indicate effectiveness, reductions in fracture risk can occur even before significant BMD changes are seen. Healthcare providers also monitor for side effects and assess overall patient health to ensure the treatment plan remains appropriate.