Management
Bisphosphonates are the mainstay of pharmacologic treatment of PD. Etidronate was the first bisphosphonate used to treat PD in the 1970s but has now been superseded by more potent agents. All of the potent bisphosphonates reduce bone turnover and are effective in treating PD, but the degree depends on the potency of agent, and the dose and duration of treatment. The most common oral treatment regimens are risedronate 30 mg/daily for 2 months or alendronate 40 mg daily for 6 months, but based on a recent study, arguably the gold standard treatment is intravenous zoledronate. In a randomised controlled trial of 349 patients with active PD (mean age 70 years, mean ALP 430 IU/L), a single dose of 5 mg of zoledronate was compared with a 2 -month course of oral risedronate. At 6 months, ALP was within the normal range in 89% treated with zoledronate and 58% with risedronate, and quality of life tended to be better with zoledronate. Two years after this treatment course, only 2% treated with zoledronate had an ALP above the normal range compared with 43% treated with risedronate, and by 6.5 years the corresponding figures were 12.5% and 62%. Bone markers at 6 months after treatment were a strong predictor of relapse. For ALP levels at 6 months of <80 IU/L, 7–8% of those treated with zoledronate had an elevated ALP subsequently, whereas in those with ALP from 80 to 120 IU/L and >120 IU/L, the corresponding percentages were 15–16% and 67%, respectively. Thus, it seems reasonable that a goal of treatment with PD is to bring bone turnover into the lower half of the normal range.
Patients who are asymptomatic with mild PD and who are not at risk of secondary complications do not need any specific treatment and can be monitored with periodic clinical review and measurement of ALP.
In patients who have extensive PD or are symptomatic, treatment with bisphosphonates should be considered. Effective treatment of active PD leads to reduced pain, improved quality of life, normal ALP and reduced activity on bone scans. On bone biopsy, new bone formed has a normal lamellar structure, but while lytic lesions heal, radiographs generally do not return to normal. There is some debate as to whether bisphosphonates can prevent complications of PD such as fracture, osteoarthritis or nerve compression. Currently, there is no evidence to suggest this, but equally such evidence is very unlikely to be acquired as it would require prolonged follow-up of patients without treatment. In the absence of such evidence, many clinicians will treat patients where they are concerned complications may develop—for example, where PD is in long bones to prevent fracture, adjacent to joints to prevent osteoarthritis and in the skull or spine to prevent nerve compression. Bones with active PD have increased metabolism and blood flow. In patients undergoing orthopaedic surgery who have active PD at the site of surgery, substantial blood loss can occur during the procedure. Treatment with bisphosphonates prior to surgery to reduce bone vascularity can be considered. Simple analgesics and non-pharmacologic treatments such as weight loss and exercise programmes are often useful in treating secondary complications of PD such as osteoarthritis.
After initial treatment, monitoring of ALP every 1–2 years is reasonable, and retreatment could be considered if symptoms recur, and/or if ALP becomes markedly elevated (>3 times the upper reference range). Many patients with mild disease affecting only one or a few bones have prolonged normalisation of ALP following a single dose of zoledronate, and this sustained remission means that the PD will not relapse within their lifetime.