Reclast is zoledronic acid and a member of the bisphosphonate group. It is administered intravenously only because when taken by mouth it is too caustic to the stomach. It is very potent and lasts for at least a year in people with normal kidney function but longer in those with lower levels of kidney function. Reclast works well and is proven to prevent as well as treat osteoporosis. It prevents fractures of the spine, hip, and peripheral skeleton in people with osteoporosis. It has benefits, side effects, and limitations that are discussed below.
Reclast US FDA Indications from the Product Label
Treatment of Osteoporosis in Postmenopausal Women
Reclast is indicated for treatment of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, diagnosed by bone mineral density (BMD) or prevalent vertebral fracture, Reclast reduces the incidence of fractures (hip, vertebral and non-vertebral osteoporosis-related fractures). In patients at high risk of fracture, defined as a recent low-trauma hip fracture, Reclast reduces the incidence of new clinical fractures.
Prevention of Osteoporosis in Postmenopausal Women
Reclast is indicated for prevention of osteoporosis in postmenopausal women.
Osteoporosis in Men
Reclast is indicated for treatment to increase bone mass in men with osteoporosis.
Reclast is indicated for the treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who are expected to remain on glucocorticoids for at least 12 months.
Paget’s Disease of Bone
Reclast is indicated for treatment of Paget’s disease of bone in men and women. Treatment is indicated in patients with Paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease.
Important Limitations of Use
The safety and effectiveness of Reclast for the treatment of osteoporosis is based on clinical data of three years duration. The optimal duration of use has not been determined. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. Patients who discontinue therapy should have their risk for fracture re-evaluated periodically.
Treatment of Postmenopausal Osteoporosis
A 3 years study of Reclast was conducted in 7736 postmenopausal women with osteoporosis whose average age was 73. All women took calcium and vitamin D3 daily.
The rate of new vertebral fractures in the placebo group was 109 per 1,000 vs. 33 per 1,000 in the Reclast group for a statistically significant relative risk reduction of 70% and an absolute risk reduction of 7.6%. To prevent 1 new spine fracture with Reclast requires treatment of 13 women like those in the study for 3 years.
The rate of new hip fractures was 25 per 1,000 in the placebo group vs. 14 per 1,000 in the Reclast subjects for a statistically significant relative risk reduction of 41% and an absolute risk reduction of 1.1%. To prevent 1 new hip fracture with Reclast in women like those in the study requires treatment of 91 for 3 years.
The rate of new peripheral fractures in the placebo group was 107 per 1,000 vs. 80 per 1,000 for a statistically significant relative risk reduction of 25% and an absolute risk reduction of 2.7%. To prevent 1 peripheral fracture with Reclast requires treating 37 women like those in the study for 3 years.
What the Reclast study tells us is women with osteoporosis similar to those in the study who take calcium and vitamin D will have about 109 in 1,000 spine fractures, 25 in 1,000 hip fracture, and 36 in 1,000 peripheral fractures over the next 3 years without any treatment. If these same women were placed on Reclast their absolute fracture rates would fall in the spine to 33 in 1,000, in the hip to 14 in 1,000, and in the peripheral skeleton to 13 in 1,000.
Treatment with Reclast resulted in a 6.7% increase in BMD at the lumbar spine, 6.0% at the total hip, and 5.1% at the femoral neck compared to placebo.
Osteoporosis in Men
Reclast increased bone density in a study of 302 men with osteoporosis from a variety of causes by about 6% after 2 years of therapy.
Treatment and Prevention of Glucocorticoid-Induced Osteoporosis
Reclast was tested in 833 men and women, average age of 54 who were chronically on 7.4 mg+ of prednisone or its equivalent daily for 1 year. All patients took vitamin D and calcium supplements. The bone density increased significantly in the spine by 4.1% in the Reclast group demonstrating its ability to prevent bone loss due to glucocorticoids.
Reclast Side Effects
Acute Renal Failure, Death
- The most serious acute reaction to Reclast is death. This occurred in about 80 people who received the drug soon after it was released for marketing and was due to acute renal failure in every case. The people harmed has pre-existed class IV chronic kidney disease meaning they had lost about 75% of the renal function due to other factures before being treated with Reclast. Reclast is hard on the kidney anyway but in people with CKD IV or worse it is hard control without careful and knowledgeable management. Today, almost everyone prescribing Reclast knows to check the kidney function before administering it and if the kidney function is not better than a eGFR for estimated Glomerular Filtration Rate of 35 ml/min or higher, then it should not be given. It could still be given by an expert if there was not other options, however there is and that is Prolia. Prolia or denosamab can be given to people on dialysis or in advanced staged CKD but again an expert should do this.
Fever, Muscle Aches, Head Ache during and after the Reclast Infusion
This is the most common acute phase reaction. We say this in the Reclast study subjects and we say the same reaction when using other bisphosphonate drugs intravenously for treatment of osteoporosis in the past. The study patient receiving IV Reclast had the following acute phase reactions:
- Fever (18%)
- Myalgia (9%)
- Flu-like symptoms (8%)
- Headache (7%)
- Arthralgia (7%)
In most these side effects cleared up within the first 3 days but in a few it took several weeks. We learned how to prevent these side effects from occurring years ago when administering bisphosphonates IV for osteoporosis treatment in the clinic that had the same acute phase reaction.
Several simple steps can be taken to avoid these problems. The first is to instruct the patient to hydrate well the day and night before having the infusion meaning drinking water and liberal use of sodium. The second is to give Reclast in a 250 cc bag of normal saline instead of a 100 cc bag IV over an hour instead of 15 minutes. The third is to pre-treat the patient with 25 mg of Benadryl and 1,000 mg of Tylenol by mouth about 30 minutes before the infusion starts. This has always worked for me. If the patient begins to have an acute phase reaction despite taking the above actions and is still in the clinic, giving 20 mg of solumedrol IV promptly halts the reaction.
Osteonecrosis of the Jaw
Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates, including zoledronic acid. Most cases have been in cancer patients treated with intravenous bisphosphonates undergoing dental procedures. Some cases have occurred in patients with postmenopausal osteoporosis treated with either oral or intravenous bisphosphonates.
ONJ is rare in osteoporosis patients treated with any of the bisphosphonates. It is really a problem for cancer patients that are being treated with these same drugs but at much higher doses and in combination with other chemo drugs and glucocorticoids that predispose to ONJ. When ONJ occurs in the osteoporosis patient it is usually the lease sever grade that does not require treatment. Good dental hygiene is recommended as the best strategy to prevent ONJ and that is sound health advice for all anyway.
Atypical Subtrochanteric and Diaphyseal Femoral Fractures
Atypical, low-energy, or low trauma fractures of the femoral shaft have been rarely reported in bisphosphonate-treated patients. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates.
These odd fractures have been observed in people very rarely. They occur mostly in women treated with oral alendronate, a bisphosphonate like Reclast. It has been seen in people treated with Reclast but not nearly as often as with alendronate. It is a rare side effect. Thigh pain precedes the fracture by a couple of months in many patients. In 40%, both femurs are involved. X-ray can diagnose it and if found early, the fracture can be stabilized with a rod that prevents the femur from breaking.
In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain have been infrequently reported in patients taking bisphosphonates, including Reclast. The time to onset of symptoms varied from one day to several months after starting the drug.
I think musculoskeletal pain occurs with all osteoporosis therapies by different mechanisms but in my opinion, for the same reason. These drugs either cause the skeleton to halt giving up calcium and magnesium from its storehouse by inhibiting osteoclastic bone absorption or the cause new bone growth that places higher demands upon the serum and diet to provide calcium for bone to be made. The result of both these mechanisms is less calcium and magnesium for muscles, ligaments, tendons, and the cartilage that line the joints. These tissues rely on these minerals heavily for their function and health. If these mineral resources are limited, the affected tissues suffer and one of the ways they do so is by going into spasm leading to a buildup of lactic acid followed by burning, pain, and cramping.
Optimizing calcium, magnesium and vitamin D nutrition is my approach to this issue when it happens. Splitting the dose of minerals between the morning and bedtime is important but the vitamin D can be taken once daily. A typical suggestion I make for patients complaining of this is to take 1 calcium citrate tablet and one 500 mg magnesium oxide capsule in the morning with vitamin D3 plus 1 calcium citrate tablet and 1 magnesium oxide capsule at night before bed. Often this simple remedy resolves the problem.