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Table 1 Detailed inclusion and exclusion criteria

From: Denosumab for treating periprosthetic osteolysis; study protocol for a randomized, double-blind, placebo-controlled trial

Inclusion criteria Exclusion criteria
Age 40–85 years For women of childbearing potential: Subject refuses to use 1 highly effective method of contraception (contraceptive pill, intra uterine contraceptive device) for the duration of the study and for 10 months after the last dose of study medication.
Short Portable Mental Status Questionnaire (SPMSQ) also named Pfeiffertest ≥7 For males with a partner of childbearing potential: Subject refuses to use 1 highly effective method of contraception for the duration of the study and for 10 months after the last dose of study medication.
Male and females For males with a partner who is pregnant: Subject refuses to use a condom for the duration of the study and for 10 months after the last dose of study medication.
The primary THA performed between 7 to 20 years before inclusion. Pain in the operated hip (because the presence of hip pain in combination with an osteolytic lesion is an indication for revision surgery). VAS >3
The primary THA performed due to osteoarthritis or congenital dysplasia of the hip. Previous revision surgery of the hip i.e. exchange of any inplant after the primary surgery
Uncemented cup fixation Inflammatory arthritis
Baseline osteolytic lesion of at least 4 cm3 and at most 40 cm3around an uncemented acetabular component with a polyethylene liner. Previous participation in clinical trials with denosumab or administration of commercial denosumab (Prolia™ or Xgeva™)
Participant is willing and able to follow study protocol and has provided informed consent prior to any study specific procedures. Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial (s), or subject is receiving other investigational agent (s).
  Treatment with any intravenous bisphosphonate, fluoride (except for dental treatment) or strontium ranelate within 5 years prior to inclusion.
  Treatment with any oral bisphosphonate within 1 year prior to inclusion.
  Treatment with cortisol or cytostatic drugs within 6 months prior to inclusion.
  Administration of any of the following treatments 3 months prior to screening:
  For women of childbearing potential: Subject refuses to use 1 highly effective method of contraception (contraceptive pill, intra uterine contraceptive device) for the duration of the study and for 10 months after the last dose of study medication.
  For males with a partner of childbearing potential: Subject refuses to use 1 highly effective method of contraception for the duration of the study and for 10 months after the last dose of study medication.
  For males with a partner who is pregnant: Subject refuses to use a condom for the duration of the study and for 10 months after the last dose of study medication.
  Pain in the operated hip (because the presence of hip pain in combination with an osteolytic lesion is an indication for revision surgery). VAS >3
  Previous revision surgery of the hip i.e. exchange of any inplant after the primary surgery
  Inflammatory arthritis
  Previous participation in clinical trials with denosumab or administration of commercial denosumab (Prolia™ or Xgeva™)
  Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial (s), or subject is receiving other investigational agent (s).
  Treatment with any intravenous bisphosphonate, fluoride (except for dental treatment) or strontium ranelate within 5 years prior to inclusion.
  Treatment with any oral bisphosphonate within 1 year prior to inclusion.
  Treatment with cortisol or cytostatic drugs within 6 months prior to inclusion.
  Administration of any of the following treatments 3 months prior to screening:
    Anabolic steroids or testosterone
    Glucocorticosteroids (≥5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of ≥ 50 mg)
    Calcitonin
    Calcitriol or vitamin D derivatives [vitamin D contained in supplements or multivitamins is allowed]
    Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin
    Chronic systemic ketoconazole, ACTH (adrenocorticotrophic hormone), cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists.
    Androgen deprivation therapy
  Hypocalcaemia.
  Bone metabolic disorders (such as OI, PHPT, Paget)
  History of osteonecrosis of the jaw and/or recent tooth extraction or dental surgery; or planned invasive dental proceedures during the study
  Serum 25-OH D <20 ng/ml
  Significant malabsorption including Celiac Disease, Short Bowel Syndrome, Crohn’s Disease, Previous Gastric Bypass.
  Active cancer and/or malignancy in last 5 years (except cervical carcinoma in situ or basal cell carcinoma)
  History of solid organ or bone marrow transplant.
  Hypersensitivity to any components of study drug.
  Intolerance to calcium supplements.
  Pregnancy and/or currently lactating.
  Significantly impaired renal function as determined by a derived glomerular filtration rate (GFR) using Cockcroft Gault formula of ≤ 30 mL/min/1.73 m2
  Elevated transaminases ≥ 2.0 × upper limit of normal (ULN); Elevated total bilirubin (TBL) > 1.5 × ULN.
  Any condition or illness (acute, chronic, or history), which in the opinion of the Investigator might interfere with the evaluation of efficacy and safety during the study or may otherwise compromise the safety of the subject.
  Hypocalcaemia.
  Bone metabolic disorders (such as OI, PHPT, Paget)
  History of osteonecrosis of the jaw and/or recent tooth extraction or dental surgery; or planned invasive dental proceedures during the study
  Serum 25-OH D <20 ng/ml
  Significant malabsorption including Celiac Disease, Short Bowel Syndrome, Crohn’s Disease, Previous Gastric Bypass.
  Active cancer and/or malignancy in last 5 years (except cervical carcinoma in situ or basal cell carcinoma)
  History of solid organ or bone marrow transplant.
  Hypersensitivity to any components of study drug.
  Intolerance to calcium supplements.
  Pregnancy and/or currently lactating.
  Significantly impaired renal function as determined by a derived glomerular filtration rate (GFR) using Cockcroft Gault formula of ≤ 30 mL/min/1.73 m2
  Elevated transaminases ≥ 2.0 × upper limit of normal (ULN); Elevated total bilirubin (TBL) > 1.5 × ULN.
  Any condition or illness (acute, chronic, or history), which in the opinion of the Investigator might interfere with the evaluation of efficacy and safety during the study or may otherwise compromise the safety of the subject.