Clinical trial: Comparing Efficacy and Safety of AryoGen Pharmed Biosimilar Denosumab 60 mg (Arylia) Versus Prolia® in Improvement of Bone Mineral Densitometry (BMD) Among Osteoporotic Postmenopausal Women (NCT03293108)

Eligibility criteria:
Inclusion Criteria:

          -  Postmenopausal women aged between 45 up to 75;

          -  Bone mineral density T score at the lumbar spine (L1-L4), femoral neck or total hip
             should be equal or less than -2.5 and equal or more than -4. (-4 ≤ T score ≤-2.5); or
             patients with high risk of fracture on the basis of FRAX criteria which according to
             osteoporosis treatment guidelines, need medicinal treatment.

          -  Ability to comprehend and willingness to sign the Informed Consent Form for this
             study;

          -  Signed informed consent with full knowledge and mental health.

        Exclusion Criteria:

          -  Lack of consent for being in the trial and not complying with an 18-months follow-up;

          -  Having hypersensitivity to denosumab or any component in the formulation (excipients
             include acetic acid, sorbitol, polysorbate 20, sodium hydroxide, water for
             injections);

          -  Malabsorption syndrome;

          -  History of thyroid surgery, parathyroid surgery or intestinal resection which has been
             caused malabsorption.

          -  Patient with CKD stage 4 and 5 should be exclude (GFR <30cc/min)

          -  Level of serum 25-(OH) vitamin D less than 20 ng/ml; (If vitamin deficiency has been
             corrected, and two tests show the level above 20 ng/ml within a month, the patient can
             be enrolled.)

          -  Pre-existing hypocalcemia (Albumin-adjusted serum calcium level less than 8 mg/dl in
             fasting specimens) which is uncorrectable;

          -  Untreated hypercalciuria (>250 mg/24h) and hypocalciuria (<100 mg/24h). If urine
             calcium level of patient is less than 100 mg per 24 hours and by vitamin D treatment
             the problem has been solved or if urine calcium level of patient is greater than 250
             mg per 24 hours, but PTH is normal, the patient can be enrolled.

          -  Presence of osteonecrosis of jaw (ONJ) risk factors including a diagnosis of cancer,
             poor oral hygiene, periodontal and/or dental diseases, having dentures; and comorbid
             disorders (anemia (hemoglobin level less than 11 g/dl, if it is corrected, patient can
             enter the study), history of diseases with coagulopathy, oral and dental infection);

          -  Malignancy;

          -  Having severe and active infections; (Severe infection is a difficult treated
             infection, like diabetic foot infection, but if the infection is treatable, after
             treatment, the patient can be enrolled.)

          -  Being bed rest (for 2 weeks during the past 3 months)

          -  A case in which the patient cannot take 1000 mg oral elemental calcium per day; (as
             supplement)

          -  A case in which bone mineral density could not be accurately measured;

          -  Conditions that influence bone metabolism, including hyperparathyroidism or
             hypoparathyroidism, hyperthyroidism or hypothyroidism, hypocalcemia, inflammatory
             rheumatologic diseases such as rheumatoid arthritis, Paget's disease of bone,
             osteomalacia that is resistant to therapy (definition of resistant to therapy: not
             being responder to 1-month administration of vitamin D).

          -  Patients will be excluded if they have one severe or more than 2 moderate vertebral
             fractures. (Severe fracture is defined as more than 50 percent vertebral height loss
             and moderate fracture is defined as 25-50 percent vertebral height loss).

          -  Use of injectable bisphosphonates within the previous 12 months;

          -  Use of oral bisphosphonates within the previous 3 months;

          -  History of severe skeletal pain with bisphosphonates;

          -  Use of parathyroid hormone or its derivatives, systemic hormone-replacement therapy,
             selective estrogen-receptor modulator, calcitonin, or calcitriol within 6 weeks before
             study enrollment.

          -  Use of corticosteroids (>5 mg/prednisone daily or equivalent for ≥ 3months), in the
             past 3 months and more.

          -  Use of heparin (more than 20,000 international units/day for 6 months and longer), in
             the past 6 months and more.

          -  Patient that is possible to be administrated corticosteroids (>5 mg/prednisone daily
             or equivalent for ≥ 3months) or heparin (more than 20,000 international units/day for
             6 months and longer) in the 18 month of the study, because of her chronic disease(s)
             such as allergy, asthma, coagulation disorders, should be excluded.
Female
No healthy subjects accepted to join the trial.
Subject must be at least 45 Years old.
Subject must be at most 75 Years

Patient description (medical language): A 55-year-old white woman comes for a routine checkup.  She has no significant medical history and does not use tobacco, alcohol, or illicit drugs.  The patient's only medication is an over-the-counter multivitamin.  Family history is notable for a hip fracture in her mother.  Blood pressure is 130/80 mm Hg and pulse is 112/min. She has occasional back pain and lives a sedentary lifestyle with the BMI of 24 Kg/m2. Plain X-ray of the spine shows mild compression fracture at the level of T10. X-ray absorptiometry studies demonstrate abnormally low bone density in the lumbar vertebrae and T-score values below -2.5, which confirms the diagnosis of osteoporosis.

Patient description (patient's own words): I'm a 55-year-old white woman and I recently visited my family doctor. I don't smoke anything or drink. I don't have any remarkable medical history. I only use over-the-counter multivitamins to keep myself fresh and energized. My mom had a hip fracture. The doctor took my blood pressure and it was 130/80 and my pulse was 112/min. I have annoying back pain from time to time and to be honest I don't exercise much or move much. My BMI is 24. I did a spine X-ray a while ago and my doctor showed me that I have a fracture on one of my vertebrae. I also have a low bone density in my lumbar vertebrae and T-score values below -2.5. The doctor diagnosed me with osteoporosis.

Does the patient match the trial criteria? Entailment