Study of Pamidronate for the Prevention of Heterotopic Ossification
Information source: University Hospital, Basel, Switzerland
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Heterotopic Ossification
Intervention: Pamidronate (AREDIA) (Drug)
Sponsored by: University Hospital, Basel, Switzerland
Official(s) and/or principal investigator(s):
philipp schuetz, MD, Principal Investigator, Affiliation: University Hospital, Basel, Switzerland
Christian Meier, MD, Study Director, Affiliation: University Hospital in Basel
The purpose of this study is to determine whether Bisphosphonates in comparison to radiation
therapy are effective in the prophylaxis and treatment of heterotopic ossification in high
Official title: Study Into the Effect of Pamidronate for the Prevention of Heterotopic Ossification in High-risk Patients: A Randomized Controlled Trial
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Primary endpoint is the radiological Heterotopic Ossification recurrence rate.
Secondary outcome: Secondary endpoints are the clinical, functional and biochemical outcome (as assessed by several clinical and laboratory markers).
BACKGROUND: The acquired form of heterotopic ossification (HO) is the most common type of
extraskeletal ossification and usually precipitated by a trauma such as total hip
arthroplasty [THA] or spinal cord injury. After THA the incidence of HO is as high as 50%,
but may reach up to 90% in high risk populations leading to severe functional impairment
with ankylotic loss of joint mobility. Nonsteroidal anti-inflammatory drugs (NSAIDs) and
external radiation have been used in preventing HO. Specifically, patients with surgical
resection of HO at the hip have a high postoperative relapsing rate. Best results were
observed after prophylactic radiation treatment with disease recurrence in 33-45% of
patients. Data on the effect of bisphosphonates in the prevention of postoperative HO are
scarce and mainly limited to the use of the first generation bisphosphonate etidronate. In a
retrospective observational study we observed a marked beneficial effect of pamidronate
infusions: none of the high risk patients with established HO undergoing surgical removal
presented with disease recurrence.
AIM: We therefore aim to prospectively confirm our findings and to evaluate the efficacy of
pamidronate for the prevention of recurrent HO after surgical removal of ipsilateral HO.
Clinical, biochemical and radiological treatment outcome will be compared to standard
clinical practice using preoperative external radiation.
ENDPOINTS: Primary endpoint is the radiological HO recurrence rate. Secondary endpoints are
the clinical, functional and biochemical outcome (as assessed by several clinical and
METHODS: This prospective, randomized trial will be carried out at the University Hospital
in Basel/Buderholz in collaboration with the Orthopedic Clinic of the Swiss Paraplegic
Centre in Nottwil. Patients who are admitted to the one of the participating orthopedic
clinics for removal of HO at the hip will be included in the study. A total number of 40
consecutive patients will be recruited (recruitment phase 24 months) and randomized in a
"bisphosphonate group", treated with peri- and postoperative pamidronate infusions (1. 0
mg/kg/day for 3 days) and in a "radiation group", treated with external radiation with a
single dose of 7 Gy within 24 hours prior to surgical intervention. Additionally, both
groups will be treated with NSAIDs for 14 days.
EXPECTED RESULTS: We hypothesize that in treating patients at risk, therapy with pamidronate
will be superior in reducing the recurrence rate of established HO as compared to external
radiation after surgical resection.
SIGNIFICANCE: Because of the high prevalence in selected risk patients and significant
morbidity of HO, this study will offer potential for improving the management of HO. Our
study is targeting patients with high risk to develop HO were highly effective prevention is
still lacking. Furthermore, a diagnostic marker to identify patients at risk to develop HO
would optimize disease management and would allow for early, more successful treatment.
Minimum age: 20 Years.
Maximum age: N/A.
- Consecutive patients with established HO (Brooker grade III-IV), hospitalized for
resection of HO lesions
- Age <20 years
- Vitamin D deficiency (25OH-Vitamin D <30 ng/ml)
- Renal insufficiency (Clearance <50 ml/min)
- Intolerance of bisphosphonates
- Unable to provide informed consent
Locations and Contacts
Schuetz P, Mueller B, Christ-Crain M, Dick W, Haas H. Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases. Spinal Cord. 2005 Oct;43(10):604-10.
Starting date: June 2005
Last updated: March 9, 2015