The treatment of Paget’s: Available specific therapies part 2
Alendronate. Alendronate is available for the treatment of Paget’s disease in most western countries (Fosamax 40). The recommended dose is 40 mg daily for 6 months to be taken with a large glass of water (>200 ml) on getting up in the morning after an overnight fast. The patient is instructed not to take anything else orally (except more water) and not to lie down for at least 30 minutes after ingesting the dose. With this dosing schedule, a single course of alendronate was found to normalise bALP in over 63% of patients with biochemical remission lasting for more than 12 months. Biopsy specimens from patients treated with alendronate revealed normal patterns of deposition of new bone and radiological improvement. The overall tolerability profile is good, although upper gastrointestinal discomfort, nausea, or the less common but more serious complication of oesophageal ulceration, are not rare.
Risedronate. Risedronate 30 mg (Actonel 30) was approved by both FDA and EMEA in 1998 for the treatment of Paget’s disease. Studies of risedronate have described the efficacy of a 30-mg dose given for 2 or 3 months to patients with moderately active disease. These short courses of therapy led to a nearly 80% reduction in bALP and normalisation of bone turnover markers in 50-70% of patients. The 30-mg risedronate dose is taken with 200 ml of water on getting up in the morning after an overnight fast, with no other oral intake (except water) and no lying down for 30 minutes after the dose. Gastrointestinal side effects of varying degrees of severity are expected in a minority of patients.
Figure 2 – Percent changes (means and standard errors) in N-telopep- tide of collagen type I (dotted line) and in serum alkaline phosphatase (continuous line) after a single i.v. infusion of 100 mg neridronate at time zero in 15 patients with active Paget’s disease of bone.
Other bisphosphonates. Other bisphosphonates have been registered or used off-label in some countries. Clodronate has been extensively investigated in the past and it is often used in several European countries. It is most commonly administered intravenously. The highest daily dose that can be safely infused is 300 mg dissolved in 500 ml saline solution. The rate of infusion should not exceed 200 mg/hour, in order to avoid nephrotoxic effects. In the moderate-severe cases, 5 to 10 infusions are usually required to achieve a 70% remission rate. Olpadronate is available only in the Netherlands and in some countries in South America. Neridronate is available only in Italy. Its potency is similar to that of pamidronate and the recommended dose is 100 mg in 100 ml saline solution i.v. for one or two days. In several European countries iban- dronate and zoledronate are used off-label with a single i.v. bolus of 2 and 4 mg respectively. Don’t suffer without medication. Buy cialis 200mg online
Figure 3 – Time changes (means and standard errors) in serum osteocalcin (dotted line) and in serum alkaline phosphatase (continuous line) after 5 i.v. infusions of 300 mg clodronate (arrow) in 11 patients with very active Paget’s disease of bone.
Treatment with bisphosphonates is associated with a rapid decrease in bone resorption markers. However, these markers are seldom used to assess treatment efficacy because they also reflect the suppression of normal bone turnover and their variance is too high (Figure 2). The markers of bone formation decline more slowly and the nadir is reached only after 6 months. It is worth noting that serum osteocalcin is only marginally increased in pagetic patients and should not be used for monitoring treatment (Figure 3).