Clinical trial NCT01926158: Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women
Official title: Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women: a Randomized, Double-blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hip Osteoarthritis
Keywords: Denosumab
Osteoporosis
Hip replacement
Osteoarthritis
Radiostereometric analysis (RSA)
Dual energy X-ray absorptiometry (DXA)
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Amgen
First posted: 2013-08-20
Enrollment: 65
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This randomized clinical trial will evaluate the efficacy of an antiresorptive osteoporosis drug (denosumab) in prevention of periprosthetic bone loss and in promotion of implant osseointegration (bone bonding) in postmenopausal women after total hip replacement. The investigators assume that denosumab prevents periprosthetic bone loss and enhances bone bonding of the hip stem in postmenopausal women.

Detailed description: This is a randomized, double-blind and placebo-controlled trial to evaluate the efficacy of denosumab on the biologic incorporation of cementless hip prosthesis. The study population consists of sixty-eight postmenopausal female patients, who are scheduled to have cementless total hip replacement (THA) for primary hip osteoarthritis. The patients will be randomly assigned to receive a subcutaneous injection of denosumab 60 mg or placebo four weeks before surgery and 22 weeks after surgery. The primary hypothesis is that denosumab is effective in preventing periprosthetic bone loss in the proximal femur as measured by DXA. The secondary hypothesis is that denosumab is effective in enhancement of bone bonding (osseointegration) of cementless femoral stems, as measured by model-based radiostereometric analysis.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women, age: ≥ 60 years to ≤ 85 years at randomization
* Degenerative primary hip osteoarthritis as the indication of hip replacement
* Signed informed consent

Exclusion Criteria:

* Presence of severe osteoporosis (T-score less than -4.0 and a previous fracture)
* Presence of Dorr C-type geometric change of the proximal femur
* Evidence of secondary osteoporosis
* Clinical or laboratory evidence of hepatic disease
* Laboratory evidence of hypocalcaemia
* Vitamin D deficiency (serum 25-OH(D) \< 12 ng/mL)
* Disorders of parathyroid function
* Uncontrolled hyperthyroidism or hypothyroidism
* History of malignancy, radiotherapy or chemotherapy for malignancy (except basal cell carcinoma of the skin) within the last 5 years
* History of osteonecrosis of the jaw
* History of recent tooth extraction or other dental surgery and/or invasive dental work planned in the next 2 years
* Severe asthma or chronic obstructive pulmonary disease
* History of solid organ or bone marrow transplant
* Use within 12 months of drugs that affect bone metabolism such as ant-osteoporotic agents (including SERMS), estrogens, testosterone, and anti-epileptics:

  * Cumulative dose of 500 mg prednisone or equivalent within the last 6 months
  * Ever use of oral or iv bisphosphonates
  * Ever use of strontium ranelate or fluoride
* Use of the following medications:

  * chronic systemic ketoconazole
  * androgens
  * cinacalcet
  * aluminum
  * lithium
  * protease inhibitors
  * gonadotropin-releasing hormone agonists
* Rheumatoid arthritis or any other inflammatory arthritis
* History of skeletal disorder, such as Paget's disease or osteomalacia
* Alcohol abuse
* General

  * Mental, neurological or other conditions that may affect the ability to perform functional or clinical assessments required by the protocol
  * Subjects with known sensitivity or intolerance to any of the products to be administered (calcium and D-vitamin supplements, denosumab)
  * Subject will not be available for protocol-required study visits, to the best of the subject's and investigator's knowledge
  * Any other condition that, in the judgement of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures

Primary outcomes:
measure: Periprosthetic bone mineral density (BMD)
timeFrame: 48 weeks
Secondary outcomes:
measure: Radiostereometric analysis (RSA) of prosthesis stem migration
timeFrame: 48 weeks
Other outcomes:
measure: Functional recovery
timeFrame: 48 weeks
Locations:
city: Turku
country: Finland
facility: Turku University Hospital
Study officials:
affiliation: Turku University Hospital
name: Hannu T Aro, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aro HT, Alm JJ, Moritz N, Makinen TJ, Lankinen P. Low BMD affects initial stability and delays stem osseointegration in cementless total hip arthroplasty in women: a 2-year RSA study of 39 patients. Acta Orthop. 2012 Apr;83(2):107-14. doi: 10.3109/17453674.2012.678798. Epub 2012 Apr 11.
citation: Moritz N, Alm JJ, Lankinen P, Makinen TJ, Mattila K, Aro HT. Quality of intertrochanteric cancellous bone as predictor of femoral stem RSA migration in cementless total hip arthroplasty. J Biomech. 2011 Jan 11;44(2):221-7. doi: 10.1016/j.jbiomech.2010.10.012. Epub 2010 Nov 11.
citation: Alm JJ, Makinen TJ, Lankinen P, Moritz N, Vahlberg T, Aro HT. Female patients with low systemic BMD are prone to bone loss in Gruen zone 7 after cementless total hip arthroplasty. Acta Orthop. 2009 Oct;80(5):531-7. doi: 10.3109/17453670903316801.
citation: Makinen TJ, Alm JJ, Laine H, Svedstrom E, Aro HT. The incidence of osteopenia and osteoporosis in women with hip osteoarthritis scheduled for cementless total joint replacement. Bone. 2007 Apr;40(4):1041-7. doi: 10.1016/j.bone.2006.11.013. Epub 2007 Jan 17.
citation: Makinen TJ, Koort JK, Mattila KT, Aro HT. Precision measurements of the RSA method using a phantom model of hip prosthesis. J Biomech. 2004 Apr;37(4):487-93. doi: 10.1016/j.jbiomech.2003.09.004.
citation: Nazari-Farsani S, Finnila S, Moritz N, Mattila K, Alm JJ, Aro HT. Is Model-based Radiostereometric Analysis Suitable for Clinical Trials of a Cementless Tapered Wedge Femoral Stem? Clin Orthop Relat Res. 2016 Oct;474(10):2246-53. doi: 10.1007/s11999-016-4930-0. Epub 2016 Jun 22.