Review question

We wanted to find out if using bisphosphonate treatment was better or worse than dummy treatment (placebo) to relieve bone pain in people with Paget’s disease of bone and determine if treatment could prevent complications. We also wanted to discover which bisphosphonates were better.

What is Paget’s disease of bone and what are bisphosphonates?

Paget’s disease of bone is a chronic problem which usually affects one or a few bones. Paget’s disease causes bone renewal and repair to become abnormal; bones become weak enlarged and misshapen, leading to pain, fractures and arthritis in joints close to affected bones.

Bisphosphonates are medications that slow down the bone remodelling process.

Search date

March 2017.

Study characteristics

We included 20 studies that involved 3168 people. Of these, 10 studies (801 people) compared bisphosphonates with placebo. Studies included elderly people; slightly more participants were men; and nearly all had raised blood serum markers of bone turnover. Fourteen studies recruited participants from hospitals, outpatient and general practitioner clinics. Studies were performed in USA, Canada, UK, Europe; Australia, New Zealand and Argentina.

What are the effects of bisphosphonates in people with Paget’s disease of bone?

Bisphosphonates probably help to relieve bone pain. Pain relief is probably better with zoledronate than pamidronate or risedronate. Results were similar across studies.

We are uncertain if bisphosphonates can prevent bone fractures.

Effects on quality of life, need for orthopaedic surgery and hearing loss prevention were not reported in studies that compared bisphosphonates with placebo.

What are the side effects of bisphosphonates in people with Paget’s disease of bone?

Most studies did not report details about drug-related side effects and complications. Bisphosphonates may make little or no difference in side effects except for temporary fever or tiredness with intravenous treatments and mild gastrointestinal side effects with oral medications. Severe side effects causing treatment discontinuation were rare.

What happens to people with Paget’s disease of bone treated with bisphosphonates?

Pain

We found that of 100 adults with Paget’s disease of bone, nine would experience complete pain relief if they took bisphosphonates for six months compared with 31 people (23% more) not taking bisphosphonates.

Side effects

We found that of 100 adults with Paget’s disease of bone, 48 would experience side effects if they took bisphosphonates for six months compared with 64 (11% more) not taking bisphosphonates.

The number of people who stopped treatment due to side effects were the same for the bisphosphonate and placebo groups (4/100).

Quality of evidence

Pain relief data provided moderate-quality evidence; but data on fractures was assessed as providing very low-quality evidence. Data on side effects provided low-quality evidence; treatment discontinuation data provided moderate-quality evidence. Evidence was downgraded mainly due to limited data and concerns about study design.

Study funding sources

Eleven studies were funded by drug manufacturers. Four studies were funded by government agencies or charities. Data on funding sources were not provided or unclear in five studies.