Osteoporosis in Primary Hyperparathyroidism

Management of Osteoporosis in Patients With Primary Hyperparathyroidism

Investigators will prospectively include 40 postmenopausal women with secondary osteoporosis due to primary hyperparathyroidism who have refused surgery. Participants will be randomized in two groups and treated either with zoledronic acid 5 mg iv once a year or with denosumab 60 mg sc every 6 months. Investigators will compare the effect of both drugs on bone turnover markers and basic laboratory parameters after 3, 12 and 24 months of treatment, and on the bone mineral density after 12 and 24 months of treatment. All participants will take cholecalciferol 800 - 1000 IU daily.

Study Overview

• Status: Enrolling by invitation
• Conditions: Primary Hyperparathyroidism; Osteoporosis
• Intervention / Treatment: Drug: Denosumab 60 MG/ML Prefilled Syringe [Prolia]; Drug: Zoledronic Acid

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Endocrinology Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women (>12 months after last menstrual period) with primary hyperparathyroidism and with osteoporosis on Dual Energy Xray Absorptiometry (DXA) (according to International Society for Clinical Densitometry (ISCD) - criteria) and/or osteoporotic fracture of the vertebra or hip

Exclusion Criteria:

• The patient is not able to give informed consent
• other classic complications of primary hyperparathyroidism (e.g. kidney stones, renal insufficiency)
• serum albumin-corrected calcium level > 2.85 mmol/L (except when the patient is reluctant to undergo surgical treatment)
• osteoporosis treatment less than a year ago, less than two years ago in the case of oral bisphosphonate, less than three years ago in the case of parenteral bisphosphonate
• bilateral hip endoprosthesis
• additional causes for secondary osteoporosis (other than vitamin D deficiency) and pathological laboratory findings that are incompatible with the Summary of Product Characteristics (SmPC) of both medicines
• cancer, except if in stable remission of more than 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: denosumab; denosumab 60 mg subcutaneously every 6 months	Drug: Denosumab 60 MG/ML Prefilled Syringe [Prolia]; denosumab 60 mg subcutaneously every 6 months; Other Names: Xgeva
Active Comparator: zoledronic acid; zoledronic acid 5 mg intravenously once a year	Drug: Zoledronic Acid; zoledronic acid 5 mg intravenously once a year; Other Names: Aclasta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral density after one year of treatment	Dual-energy X-ray absorptiometry (DXA)	one year
CTX after 3 months of treatment	Unit of Measure: pmol/L	3 months
Corrected calcium after 3 months of treatment	Unit of Measure: mmol/L	3 months
Bone mineral density after two years of treatment	Dual-energy X-ray absorptiometry (DXA)	two years
CTX after 12 months of treatment	Unit of Measure: pmol/L	one year
CTX after 24 months of treatment	Unit of Measure: pmol/L	two years
PINP after 3 months of treatment	Unit of Measure: µg/L	3 months
PINP after 12 months of treatment	Unit of Measure: µg/L	one year
PINP after 24 months of treatment	Unit of Measure: µg/L	two years
Bone-specific alkaline phosphatase (BAP) after 3 months of treatment	Unit of Measure: µg/L	3 months
Bone-specific alkaline phosphatase (BAP) after 12 months of treatment	Unit of Measure: µg/L	one year
Bone-specific alkaline phosphatase (BAP) after 24 months of treatment	Unit of Measure: µg/L	two years
Corrected calcium after 12 months of treatment	Unit of Measure: mmol/L	one year
Corrected calcium after 24 months of treatment	Unit of Measure: mmol/L	two years

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Investigators: Principal Investigator: Tomaz Kocjan, MD, PhD, UMC Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2019
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: September 2, 2019
• First Submitted That Met QC Criteria: September 7, 2019
• First Posted (Actual): September 11, 2019

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: osteoporosis; zoledronic acid; primary hyperparathyroidism; denosumab
• Additional Relevant MeSH Terms: Metabolic Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Parathyroid Diseases; Bone Diseases; Bone Diseases, Metabolic; Hyperparathyroidism; Hyperparathyroidism, Primary; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid; Denosumab
• Other Study ID Numbers: 11111 (DAIDS ES Registry Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Bone mineral density, bone turnover markers and basic laboratory results will be shared.
• IPD Sharing Time Frame: The data will become available in 3 years. They will be available for 5 years.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No