Osteoporosis is a systemic disorder of bone metabolism characterized by decreased bone mass, degradation of bone microstructure, and increased bone fragility resulting in increased risk of fracture. Osteoporotic fractures are the most serious consequence of osteoporosis.
Anti-osteoporotic drug therapy can reduce the incidence of osteoporosis-related fractures, but its long-term therapeutic effects are controversial.
Currently, the commonly used anti-osteoporosis drugs include the following.
1, vitamin D, calcium, etc., is the first-line drug for the prevention of osteoporosis.
2, anti-bone resorption drugs: such as bisphosphonates, estrogen, selective estrogen receptor agonists (represented by raloxifene) and calcitonin, etc. These drugs can inhibit osteoclast bone resorption and slow down the process of bone loss.
3, pro-bone formation drugs: such as parathyroid hormone, teriparatide, fluoride, these drugs can promote the osteoblast bone formation effect.
4, other drugs: such as statins, denosumab, etc.
Are the anti-fracture effects of anti-osteoporosis drugs long-lasting?
The anti-osteoporotic fracture effect of many drugs is most pronounced within the first year of treatment when compared to placebo controls.
To observe the efficacy of prolonged drug treatment, many trials have been conducted with extensions.
Are there risks associated with discontinuing anti-osteoporotic drug therapy?
The prognosis after discontinuation of treatment varies markedly from drug to drug. A few examples are briefly listed.
1. Discontinuation of anti-osteoporosis treatment resulted in a decrease in bone mineral density, which was more pronounced in patients on estrogen replacement therapy.
In 81 patients studied, after taking combined estrogen (0.625 mg/d) for two consecutive years and then switching to placebo for one year, follow-up revealed a 4.5% and 2.4% decrease in bone mineral density in the spine and femoral rotor ridge, respectively. Estrogen replacement therapy reduced the occurrence of hip and spine, and the lumbar spine BMD decreased by 2.4% after stopping raloxifene for one year.
Bone mass also decreases after stopping denosumab treatment, with one study finding the most significant decrease in bone mineral density one year after stopping treatment.
3. In the HORIZON clinical study for zoledronic acid, patients were treated with zoledronate for 3 years and then some patients were treated with placebo for 3 years. At the end of the study, a mild decrease in BMD was found in the group that switched to placebo treatment compared to the group taking zoledronate for 6 years, but there was no significant difference in bone resorption markers.
Is it harmful to prolong the duration of anti-osteoporosis drug treatment?
Anti-osteoporosis drugs have many adverse effects, such as gastrointestinal upset with oral bisphosphonates, nephrotoxicity with intravenous bisphosphonates, and increased risk of venous thrombosis with raloxifene, among others. However, there is no evidence that the incidence of such adverse reactions increases with the duration of drug use.
1. One of the more serious complications of intravenous bisphosphonates in people with severe bone disease is osteonecrosis of the jaw. The incidence has been reported in the United States to be between 1/10,000 and 1/100,000. To date, however, there is insufficient evidence to suggest that bisphosphonates increase the incidence of osteonecrosis of the jaw. The 2191 patients who have been using these drugs consistently for less than 2.5 years have not had this complication.
2. Two cases of osteonecrosis of the jaw were found in 2343 patients treated with denosumab for 6 years. Cases of mid-femoral fractures caused by denosumab have been confirmed, but the occurrence of fractures may be related to the length of treatment.
It can be seen that side effects of anti-osteoporosis drugs do exist, but are very rare.
In the course of osteoporosis treatment, it is important to avoid two misconceptions
1. “There is no evidence that the anti-osteoporotic effect will last more than 5 years, so treatment should be stopped.”
Physicians who hold this view do not consider the patient’s high risk of fracture.
2. “Like hyperlipidemia, osteoporosis is a chronic disease and medication cannot be stopped; anti-osteoporosis treatment is lifelong.”
Unlike other chronic disease treatments, anti-osteoporosis treatment leads to changes in bone weight or structure that will not be reversed.
Therefore, our treatment should follow the principle of individualization.
So what criteria should be used to determine the treatment plan?
The answer is that the long-term treatment plan for patients with osteoporosis depends on the patient’s specific situation and the protocol of the initial treatment. The specific clinical situation is treated as follows.
1. An elderly and frail female patient should consider whether there is a combination of neurological disease or a previous history of fracture to determine the course of anti-osteoporosis drug therapy. Risk of fracture, history of previous fractures, bone mineral density, and age are all indicators to assess whether an individual needs anti-osteoporosis medication and can also be used to determine the course of treatment.
2. Patients are at a higher risk of having another fracture within a short period of time after the first fracture, so receiving medication within a short period of time after the initial fracture is a better choice. However, as the risk of re-fracture decreases over time, how does one decide the duration of anti-osteoporosis drug therapy for a patient at this time?
BMD is a good predictor of a patient’s risk of re-fracture. It has also been shown that persistent osteoporosis of the femoral neck predicts the need for long-term anti-osteoporosis treatment.
3. Since BMD can help doctors determine whether a patient needs a longer treatment course, is BMD itself an indicator to evaluate the efficacy of anti-osteoporosis treatment?
The answer is not certain. Because the relationship between the anti-osteoporosis effect of drugs such as alendronate, risedronate and raloxifene and the change of BMD caused by the drugs themselves has not been confirmed, but zoledronate and denosumab have been verified. Compared to bisphosphonates, denosumab can increase BMD to a large extent, with a higher likelihood of BMD attainment.
For severe patients with very low BMD, a combination treatment regimen can be used to correct BMD values (e.g. teriparatide or osteosclerosis protein inhibitors for initial treatment plus other classes of drugs to prolong the therapeutic effect).
4. Because of the significant differences in response to discontinuation of different anti-osteoporosis drugs, not all patients must stop treatment on schedule.
For patients treated with bisphosphonates the duration of treatment can be extended according to the patient’s condition, but not for patients on estrogen replacement therapy. Patients with fracture loss who discontinue drug therapy must be monitored regularly for bone resorption markers as well as bone mineral density.
5. The decision to extend therapy must be based on an assessment of fracture risk.
Treatment with bisphosphonates can be discontinued for 3-5 years. However, in patients with a high fracture risk, discontinuation of therapy is not a wise choice, but the possibility of drug side effects must be considered.