Clinical trial NCT02304757
Conditions: Differentiated Thyroid Cancer Osteoporosis
Keywords: differentiated thyroid cancer bone mineral density thyroid stimulating hormone suppression
Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Start date: 2015-01-01; Completion date: 2019-12-30
Enrollment: 142 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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:
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.

Arms: arm 1: 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. arm 2: 70mg po every week for 12 months.
Interventions: intervention 1: 99Tc-MDP intervention 2: Fosamax
Intervention descriptions: intervention 1: 99Tc-MDP, H20000218 intervention 2: H20080172

Protocol documents:
Prot_SAP_000.pdf: 
99Tc-MDP in Postmenopausal Women With Differentiated Thyroid Cancer and 
Osteoporosis 
 
Trial registration: NCT02304757 
April 16，2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Study Protocol  
Study Type: Interventional 
Study Design: Treatment, Parallel Assignment, Single Blind (Outcomes Assessor), 
Non-Randomized, Efficacy Study 
Patients recruitment 
This was an open-label, prospective non-randomized study carried out in three 
centers (ClinicalTrials.gov ID: NCT02304757) from November 2015 to December 
2019. Postmenopausal women are eligible in the study fulfilling all the following 
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. 
We excluded patients considering the following criteria: (1) patients having 
medications for OS before TSH suppression treatment; (2) secondary OS; (3) severe 
liver or kidney disease; (4) myelosuppression; (5) digestive disease; (6) 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. 
TSH suppression treatment  
TSH suppression treatment was based on the risk stratification of DTC using 
levothyroxine (L-T4) as recommended 
Treatment protocol for osteopenia and osteoporosis 
Patients with OS were divided into 99Tc-MDP and alendronate treatment groups.  
1. 99Tc-MDP treatment group: 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.  
2. Alendronate treatment group: 70mg alendronate (Merck & Co., Darmstadt, 
Germany) was administered orally once a week for 12m.  
Laboratory assays 
Bone alkaline phosphatase (ALP), osteocalcin and propeptide of type I 
procollagen (PINP), and C-terminal telopeptide of type I collagen (CTX) were all 
determined by enzyme-linked immunosorbent assay (Modular E170, Hoffmann-La 
Roche, Basel, Switzerland). Free T3, free T4, thyroid stimulating hormone (TSH) was 
measured using a time-resolved immunofluorometric assay (Anytest, sym-bio 
lifescience co., ltd, Shanghai, China). 25(OH) D, parathyroid hormone (PTH), serum 
calcium and phosphorus and other laboratory tests were measured as routine at 
baseline and 12m. 
Analysis of knee relief, QOL and adverse reaction 
Lysholm knee (LYS) rating scale was used to evaluate the knee function at 
baseline and 12m. QOL in patients with OS was measured with a 36-item Short Form 
Health Status Survey questionnaire (SF-36) at baseline and 12m. SF-36 including four 
physical and fundamental items were calculated which represent the deviation from 
the reference population. The higher score by SF-36 and LYS means a better QOL and 
knee function. A treating physician reviewed the clinical results and any discomfort at 
each visit. 
Statistical Analysis Plan 
The predetermined primary end point was the difference in the change in BMD 
of the lumbar spine between the two groups. Sixty four sample size was assumed to 
achieve 80% power to detect non-inferiority using a one-sided two sample t-test. The 
margin of non-inferiority is 0.5% percent. The true difference between the means is 
assumed to be 0. The significance level (alpha) of the one sided test is 0.025. The data 
were drawn from population with standard deviations of 0. Consider the 10% loss of 


follow-up rate, group sample size was 70 cases. 
Continuous data are expressed as the mean ± standard deviation. Independent 
sample t-test by SPSS 22 was used to compare the basic information, clinical 
characteristics within groups at baseline and the difference values of BMD between 
that at baseline and 6m and 12m after treatment. Differences in BMD, QOL by SF-36 
questionnaire, bone turnover marks and other laboratory results were determined 
using a paired t-test (one-sided tests) and Mann-Whitney U test. A Fisher exact test 
was used to compare the adverse events. Pearsman Rho was used to analyze the 
correlation of lumbar uptake of Na18F and BMD/T value by DXA. P value <0.05 was 
considered statistically significant.