99Tc-MDP in Postmenopausal Women With Differentiated Thyroid Cancer and Osteoporosis

Study Overview
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Brief Summary
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Postmenopausal women with differentiated thyroid cancer (DTC) taking suppressive doses of levothyroxine (L-T4) are thought to have accelerated bone loss and increased risk of osteoporosis. Therefore, the investigators try to investigate the effects of 99Tc-MDP,alendronate sodium in postmenopausal women with DTC under TSH suppression and osteoporosis.

Detailed Description
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Differentiated thyroid cancer (DTC) has become one of the most common endocrine malignancies. According to American Thyroid Association (ATA) and Chinese Thyroid Association (CTA), most of DTC patients undergo total or near total thyroidectomy, radioiodine ablation and TSH (thyroid stimulating hormone) suppression. Osteoporosis (OS) and fractures are important comorbidities in patients with DTC, with potential negative impact on quality of life (QOL) and survival. The main determinant of skeletal fragility in DTC is the TSH suppression. Postmenopausal women with DTC under TSH suppression therapy are more vulnerable to OS. Technetium-99 methylene diphosphonate (99Tc-MDP) is a decay product of 99mTc-MDP (used for bone scintigraphy) and a novel bisphosphonates, which has been used in China for diseases like rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteochondral lesions of the talus, etc. However, as a member of bisphosphates, little attention has been paid to its anti-OS effect for DTC under TSH suppression.

Official Title
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Prospective Trial of 99Tc-MDP and Fosamax in Postmenopausal Women With Differentiated Thyroid Cancer and Osteoporosis Treated With Supraphysiological Doses of Thyroid Hormone

Conditions
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Differentiated Thyroid Cancer, Osteoporosis

Intervention / Treatment
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* Drug: 99Tc-MDP
* Drug: Fosamax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) They were pathologically diagnosed with DTC including papillary or follicular carcinoma. (2) They received a near total thyroidectomy and radioiodine treatment. (3) TSH suppression should be at least one year before the study. (4) Bone mineral density (BMD) in lumbar spine and/or hip was tested by Dual-energy X-ray absorptiometry (DXA) at baseline, 6 month (m) and/or 12m follow up. 5) The diagnosis of osteoporosis was T-score ≤-2.5 SD at the lumbar spine, or hip. Exclusion Criteria: patients having medications for osteoporosis before TSH suppression treatment; secondary osteoporosis ; severe liver or kidney disease; myelosuppression; digestive disease; long term use of immunosuppressive agent, estrogen or estrogen receptor modulators. This study was approved by the Institutional Review Board of Hospital Research Ethics. All the patients were fully acquainted with their treatment and consented to participate in the clinical trial.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients with OS were divided into 99Tc-MDP and fosamax treatment groups.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 99Tc-MDP<br>15mg 99Tc-MDP were intravenously administered twice a week for 10 weeks, then once a week for 8 weeks, every two weeks for 22 weeks and monthly for another 3m. | Drug: 99Tc-MDP<br>* 99Tc-MDP, H20000218<br>* Other names: Yunke,Technetium [99Tc] Methylenediphosphonate;|
| Active Comparator: Fosamax<br>70mg po every week for 12 months. | Drug: Fosamax<br>* H20080172<br>* Other names: alendronate sodium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change of Bone Mineral Density in Lumbar and Hip | Percent change of bone mineral density in lumbar and hip by dual energy x-ray absorptiometry | baseline, 6 months, and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Turnover Markers | bone turnover markers including C-telopeptides of type I collagen (CTX), Type I N-procollagen terminal propeptide(PINP) | baseline and 12 months | 
| Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | The health related quality of life was measured by 36-item Short Form Health Status Survey questionnaire (SF-36). The minimum and maximum values were 0 and 100, respectively. Higher scores mean a better a better outcome. The questionnaire includes 36 items that can be classified into the following eight health status subscales: Physical Functioning, Physical Role Limitations, Bodily Pain, General Health Perception, Vitality, Social Functioning, Emotional Role Limitations, and Mental Health. A standardized Physical Component Summary and a standardized mental component score were calculated. The physical component summary and mental component summary represent the deviation from the reference population in Sweden. Higher scores mean a better a better outcome. | baseline, 6 months, and 12 months | 
| Side Effects | A transient rash and phlebitis, gastrointestinal reaction. | 6 months, and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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differentiated thyroid cancer, bone mineral density, thyroid stimulating hormone suppression