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Cited by 57Thyroid Cancer Diagnosis and TreatmentBone health and osteoporosis researchThyroid Disorders and Treatments

Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis

Open access
Ku, Eu Jeong, Yoo, Won Sang, Lee, Eun Kyung, Ahn, Hwa Young, Woo, Seung Hoon, Hong, Jun Hwa, Chung, Hyun Kyung, Park, Jin-Woo·2021·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/clinem/dgab539
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Abstract

Context: Because subclinical hyperthyroidism increases the risk of osteoporosis and fractures, concerns are growing about the long-term skeletal safety of TSH suppression therapy after total thyroidectomy in patients with differentiated thyroid cancer (DTC). Objective: We aimed to determine the effect of TSH suppression therapy on bone mineral density (BMD) in DTC patients. Methods: We searched PubMed, Embase, the Cochrane library, and other sources. Eligible observational studies included DTC patients who underwent TSH suppression therapy and BMD measurement. Two independent reviewers extracted data on the studies’ characteristics and outcomes and determined their risk of bias. Data were extracted from each study for postmenopausal/premenopausal women’s and men’s lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD and summed using a random-effects meta-analysis model. The weighted mean differences with 95% CIs are expressed for the differences in outcome measurements between groups. Results: Seventeen studies (739 patients and 1085 controls) were included for quantitative analysis. In postmenopausal women, TSH suppression therapy showed a significant decrease in LS BMD (-0.03; -0.05, -0.02), and a similar trend was seen in TH. In premenopausal women, TSH suppression therapy significantly increased LS BMD (0.04; 0.02, 0.06) and FN BMD (0.02; 0.01, 0.04). In men, there was no significant association between TSH suppression therapy and BMD at any site compared with the controls. Conclusion: Evidence from observational studies suggests that postmenopausal women treated with TSH suppression therapy are at risk for lower BMD. Attention should be paid to long-term skeletal safety in DTC survivors.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis found that TSH suppression therapy after thyroidectomy in DTC patients is associated with lower lumbar spine BMD in postmenopausal women, while premenopausal women showed higher lumbar spine and femoral neck BMD and men showed no significant association. The authors conclude that postmenopausal DTC survivors on TSH suppression may need regular BMD monitoring.

Key findings

  • In postmenopausal women, TSH suppression therapy significantly decreased lumbar spine BMD (408 patients and 696 controls; WMD −0.030; 95% CI, −0.020, −0.050; P < 0.001; I² = 73%), with a similar but non-significant trend at the total hip (139 patients and 304 controls; WMD −0.010; 95% CI, −0.030, 0.010; P = 0.130).
  • In premenopausal women, TSH suppression therapy significantly increased lumbar spine BMD (265 patients and 321 controls; WMD 0.040; 95% CI, 0.020–0.060; P < 0.001; I² = 2%) and femoral neck BMD (232 patients and 290 controls; WMD 0.020; 95% CI, 0.010–0.040; P = 0.009; I² = 0%).
  • In men, there was no significant association between TSH suppression therapy and BMD at any site compared with controls (lumbar spine: 94 patients and 96 controls; WMD 0.010; 95% CI, −0.030, 0.060; P = 0.570; I² = 0%).
  • The quantitative analysis included 17 studies with 739 patients and 1085 controls; 20 studies were included in the qualitative review.

Methods

  • Systematic review and meta-analysis conducted per PRISMA guidelines, searching PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov from inception to January 4, 2021.
  • Eligible studies were prospective or retrospective cohort studies and cross-sectional case-control studies of DTC patients after thyroidectomy receiving TSH suppression therapy versus healthy controls, with BMD measured by DXA at lumbar spine, femoral neck, or total hip.
  • Data were pooled using random-effects meta-analysis and expressed as weighted mean differences with 95% CIs; analyses were stratified by sex and menopausal status, with subgroup analyses by duration of TSH suppression (≤5 years vs >5 years). Risk of bias was assessed with the Risk of Bias Assessment tool for Nonrandomized Study.

Limitations

  • Stated: only one randomized controlled study was found but not included because it lacked numbers for meta-analysis; several large cohorts or prospective studies reporting osteoporosis or fracture prevalence were excluded because they did not provide accurate data; cross-sectional study results precluded confirmation of causality; only relatively small sample-sized studies and English-language literature were included; confounding factors such as physical activity could not be considered; postsurgical hypoparathyroidism was excluded or ambiguous in included studies; and exact TSH levels could not be determined, so analyses by TSH suppression level were not performed.
  • Evident from the text: postmenopausal lumbar spine analysis showed considerable heterogeneity (I² = 73%), and the included evidence is observational, limiting causal inference.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1210/clinem/dgab539

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

10 of 46 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured

  • Interpretationcitation

    The results of this meta-analysis reinforce previous reports that levothyroxine treatment-induced subclinical hyperthyroidism affects bone mineral density reduction in postmenopausal women.

    “The results of our meta-analysis reinforce the previous reports that levothyroxine treatment-induced subclinical hyperthyroidism affects BMD reduction in postmenopausal women (16,17,34) for various causes other than DTC were mixed, and the degree of TSH suppression varied considerably.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [16] Uzzan, 1996, Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis, J Clin Endocrinol Metab. source
    • cites [17] Faber, 1994, Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis, Eur J Endocrinol. source
    • cites [34] Yoon, 2019, Influence of thyroid-stimulating hormone suppression therapy on bone mineral density in patients with differentiated thyroid cancer: a meta-analysis, J Bone Metab. source

      The Results (Postmenopausal women) report lower hip and spine BMD with TSH suppression therapy, and the Discussion identifies postmenopausal women with differentiated thyroid cancer receiving that therapy as a risk group for bone loss. The paper limits its analysis to patients with differentiated thyroid cancer and says the finding is not conclusive; it does not establish a causal effect of levothyroxine-induced subclinical hyperthyroidism in postmenopausal women generally. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • Rests on an assumption: The observed associations between TSH suppression therapy and bone mineral density reflect a causal effect of TSH suppression rather than residual confounding.
  • Premisecitation

    In real clinical practice, undetectable TSH levels are usually maintained for more than 5 years after surgery.

    “However, in the real clinical world, undetectable TSH levels are usually maintained for more than 5 years after surgery (25,26).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [25] Carhill, 2015, Long-term outcomes following therapy in differentiated thyroid carcinoma: NTCTCS registry analysis 1987-2012, J Clin Endocrinol Metab. source

      The Cohort definitions section (page unavailable) describes how undetectable TSH was recorded, and the Outcomes associated with continued THST during follow-up section (page unavailable) analyzes suppression beyond five years. Neither reports that undetectable TSH was usually maintained for more than five years after surgery; searches for that duration and its frequency found no such passage. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
    • cites [26] Schneider, 2012, Effects of levothyroxine on bone mineral density, muscle force, and bone turnover markers: a cohort study, J Clin Endocrinol Metab. source

      The Sample and baseline passages describe postsurgical thyroid-cancer patients receiving TSH-suppressive therapy, and the baseline data show that some had been treated for more than five years. But the paper does not establish that undetectable TSH is usually maintained for more than five years in clinical practice: it reports suppressed TSH in a selected cohort, not a general practice pattern or continuous undetectable levels over that period. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Study design and conductcitation

    Several large cohorts or prospective studies reporting the prevalence of osteoporosis or fractures in patients with TSH suppression therapy were not included because they did not provide accurate data.

    “In addition, several large cohorts or prospective studies reporting the prevalence of osteoporosis or fractures in patients with TSH suppression therapy were not included because they did not provide the accurate data (52)(53)(54)(55).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [52] Papaleontiou, 2019, Risk of osteoporosis and fractures in patients with thyroid cancer: a case-control study in U.S. veterans, Oncologist. source
    • cites [53] Shin, 2018, J-shaped association between postoperative levothyroxine dosage and fracture risk in thyroid cancer patients: a retrospective cohort study, J Bone Miner Res. source

      The Introduction identifies this as a large nationwide study of fracture outcomes in thyroid cancer patients, and the Results report fracture incidence. It does not report fracture prevalence or directly measure TSH suppression; the Exposure section says levothyroxine dose was used as a surrogate. The decision to exclude the study is the citing authors’ own, not a finding attributed to this paper. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [54] Wang, 2015, Thyrotropin suppression increases the risk of osteoporosis without decreasing recurrence in ATA low- and intermediate-risk patients with differentiated thyroid carcinoma, Thyroid. source
  • Findingown data

    In premenopausal women with differentiated thyroid cancer after thyroidectomy, TSH suppression therapy is associated with significantly higher lumbar spine bone mineral density compared with controls (WMD 0.040; 95% CI 0.020 to 0.060; P < 0.001; I2 = 2%).

    “In premenopausal women, TSH suppression therapy significantly increased LS BMD (0.04; 0.02, 0.06) and FN BMD (0.02; 0.01, 0.04).”
    • Also stated in: § Meta-analysis Results · plain
      “On the other hand, the LS BMD in premenopausal women was significantly higher in the TSH suppression therapy group than the control group (265 patients and 321 controls, WMD 0.040; 95% CI, 0.020-0.060;P < 0.001; I 2 = 2%).”
    • Also stated in: § Discussion · plain
      “Conversely, in premenopausal women, the LS and FN BMDs were significantly higher in the TSH suppression therapy group than in the control group.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Healthy controls are an appropriate and comparable comparator to differentiated thyroid cancer patients after thyroidectomy for isolating the effect of TSH suppression therapy on bone mineral density.
    • Rests on an assumption: Bone mineral density values measured by dual-energy X-ray absorptiometry across included studies are comparable and can be pooled.
  • Findingown data

    In men with differentiated thyroid cancer after thyroidectomy, TSH suppression therapy is not significantly associated with bone mineral density at the lumbar spine, femoral neck, or total hip compared with controls.

    “In men, there was no significant association between TSH suppression therapy and BMD at any site compared with the controls.”
    • Also stated in: § Meta-analysis Results · plain
      “In men, there was no significant difference in the LS BMD (94 patients and 96 controls, WMD 0.010; 95% CI, -0.030, 0.060; P = 0.570; I 2 = 0%).”
    • Also stated in: § Meta-analysis Results · plain
      “the male TSH suppression therapy group showed a similar pattern with the control group (28 patients and 29 controls, WMD 0.010; 95% CI, -0.050, 0.070; P = 0.800; I 2 = NA) (Fig. 4).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Healthy controls are an appropriate and comparable comparator to differentiated thyroid cancer patients after thyroidectomy for isolating the effect of TSH suppression therapy on bone mineral density.
    • Rests on an assumption: Bone mineral density values measured by dual-energy X-ray absorptiometry across included studies are comparable and can be pooled.
  • Classified as probably not a substantial claim. 20
  • May combine two claims. 18

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

    “This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (18).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [18] Page, 2021, The PRISMA 2020 statement: an updated guideline for reporting systematic reviews, Bmj. source

  • May combine two claims.

    Premisecitation

    Excess thyroid hormone shortens the bone remodeling cycle, accelerates bone turnover, and consequently reduces bone mineral density.

    “Excess thyroid hormone shortens the bone remodeling cycle, accelerates bone turnover, and consequently reduces BMD (37).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [37] Raggatt, 2010, Cellular and molecular mechanisms of bone remodeling, J Biol Chem. source

      The ‘Bone Remodeling: The Process’ section discusses parathyroid hormone (PTH) and bone remodeling, but not excess thyroid hormone. Searches for thyroid hormone, hyperthyroidism, and a shortened remodeling cycle found no passage in our copy addressing the claimed sequence of effects on turnover and BMD. (LLM, conf=0.77)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The type 2 iodothyronine deiodinase pathway contributes to local T3 levels in many organs and tissues, and tissue-specific differences in type 2 iodothyronine deiodinase ubiquitination in levothyroxine-administered mice after thyroidectomy were associated with localized sensitivity to T3 and T4-TSH feedback.

    “The type 2 iodothyronine deiodinase pathway contributes to local T3 levels in many organs and tissues, and an in vivo study reported that tissuespecific differences in type 2 iodothyronine deiodinase ubiquitination in levothyroxine-administered mice after thyroidectomy were associated with localized sensitivity to T3 and T4-TSH feedback (44).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [44] Werneck de Castro, 2015, Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine, J Clin Invest. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There is much convincing evidence that asymptomatic endogenous hyperthyroidism adversely affects bones.

    “Large-scale cohort studies and meta-analyses have reported an increased risk of osteoporosis and osteoporotic fractures, so there is much convincing evidence that asymptomatic endogenous hyperthyroidism adversely affects bones (14,39).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [14] Zhu, 2020, Association of subclinical thyroid dysfunction with bone mineral density and fracture: a meta-analysis of prospective cohort studies, Endocrine. source
    • cites [39] Blum, 2015, Subclinical thyroid dysfunction and fracture risk: a meta-analysis, Jama. source

      The Discussion reports an association between endogenous subclinical hyperthyroidism and increased fracture risk, and notes that symptoms may be absent. However, the paper does not establish that it causes bone damage or report an increased risk of osteoporosis specifically; its Conclusions remain framed as an association. No page number is available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    In 4 included studies, the TSH suppression therapy group had lower bone mineral density compared with controls, and these differences were seen only in postmenopausal women.

    “In 4 studies, the group receiving TSH suppression therapy had lower BMD compared with the control group, and these differences were seen only in postmenopausal women (24,(27)(28)(29).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (24,(27)(28)(29)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • Rests on an assumption: Healthy controls are an appropriate and comparable comparator to differentiated thyroid cancer patients after thyroidectomy for isolating the effect of TSH suppression therapy on bone mineral density.
    • Rests on an assumption: Bone mineral density values measured by dual-energy X-ray absorptiometry across included studies are comparable and can be pooled.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Each included study reported that their control group was matched for possible risk factors for osteoporosis such as smoking habits, alcohol intake, menarche and menopausal status, use of calcium or vitamin D supplements, and other medications that affect BMD.

    “Third, even though each included study reported that their control group was matched for possible risk factors for osteoporosis such as smoking habits, alcohol intake, menarche and menopausal status, use of calcium or vitamin D supplements, and other medications that affect BMD”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Subclinical hyperthyroidism during TSH suppression therapy is associated with increased susceptibility to adverse cardiovascular and skeletal diseases.

    “It has been reported that the subclinical state of hyperthyroidism, in which the serum thyroid hormone level is in the normal range and the serum TSH level is suppressed (≤0.4 mU/L, especially in <0.1 mU/L) during TSH suppression therapy, has the following potential effects: reduced psychological, social and physical quality of life, and increased susceptibility to adverse cardiovascular and”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (9)(10)(11)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Publication bias was examined using funnel plots.

    “Publication bias was examined using funnel plots (Supplementary Figure 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    Confounding variables, measurement of intervention, and blinding of outcome were adequately described for all included studies.

    “Otherwise, confounding variables, measurement of intervention, and blinding of outcome were adequately described for all studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A recent meta-analysis of 17 prospective cohort studies found that subclinical hypothyroidism did not increase fracture risk but increased femoral neck bone mineral density in women, whereas subclinical hyperthyroidism increased the risk of spine and hip fractures.

    “According to a recently published meta-analysis of the associations of subclinical thyroid dysfunction with bone fractures in 17 prospective cohort studies, subclinical hypothyroidism did not increase the risk of fracture but instead showed an increase in the femoral neck (FN) BMD in women.In contrast, subclinical hyperthyroidism increased the risk of fractures in the spine and hip (14).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Zhu, 2020, Association of subclinical thyroid dysfunction with bone mineral density and fracture: a meta-analysis of prospective cohort studies, Endocrine. source

  • May combine two claims.

    Premisecitation

    A previous meta-analysis of 13 cross-sectional studies showed no significant differences in bone mineral density in premenopausal women, but postmenopausal women displayed significant bone loss compared with controls.

    “A previous metaanalysis of 13 cross-sectional studies regarding the effect of induced subclinical hyperthyroidism during long-term levothyroxine treatment on BMD showed no significant differences in premenopausal women, unlike postmenopausal women who displayed significant bone loss compared with the control groups (17).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Faber, 1994, Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis, Eur J Endocrinol. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Two authors independently confirmed study eligibility and extracted data, resolving discrepancies through discussion and, if necessary, senior reviewers' opinions.

    “Two authors (E.J.K., W.S.Y.) independently confirmed the eligibility of studies through the following steps: screening of (1) the title; (2) the abstract; and (3) the entire article, and extracting the relevant data from the qualifying studies.”
    • Also stated in: § Data Extraction · plain
      “Discrepancies were resolved through discussion and, if necessary, decided by referring to senior reviewers' opinions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Quality assessment of included studies used the Risk of Bias Assessment tool for Nonrandomized Study with 6 domains.

    “The quality assessment of included studies was conducted using the Risk of Bias Assessment tool for Nonrandomized Study consisting of 6 domains as follows: (1) selection bias for participants; (2) confounding variables; (3) the measurement of intervention (exposure); (4) the blinding of outcome assessments (detection bias); (5) incomplete outcome data (attrition bias); and (6) selective outcome”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Kim, 2013, Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity, J Clin Epidemiol. source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Two independent reviewers extracted data on study characteristics and outcomes and determined risk of bias.

    “Two independent reviewers extracted data on the studies' characteristics and outcomes and determined their risk of bias.”
    • Also stated in: § Data Extraction · plain
      “Two authors (E.J.K., W.S.Y.) independently confirmed the eligibility of studies through the following steps: screening of (1) the title; (2) the abstract; and (3) the entire article, and extracting the relevant data from the qualifying studies.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Thyroid hormones play an essential role in regulating bone metabolism, including skeletal development, linear growth, maintenance of bone mass, and efficient fracture healing.

    “Thyroid hormones play an essential role in regulating bone metabolism, including skeletal development, linear growth, maintenance of bone mass, and efficient fracture healing (13).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Bassett, 2016, Role of thyroid hormones in skeletal development and bone maintenance, Endocr Rev. source

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Three studies that did not provide specific bone mineral density values according to sex and menopausal status were used only for systematic review, not meta-analysis.

    “Because the BMD values at each site vary with gender and menopause, 3 studies that did not provide specific BMD values according to the subjects' sex and menopausal status were used only for a systematic review of the literature (22)(23)(24).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (22)(23)(24)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • Rests on an assumption: The three studies excluded from meta-analysis because they lacked sex- and menopausal-status-specific bone mineral density values do not systematically differ from included studies.

  • May combine two claims.

    Interpretationreasoning

    The lack of consistency among studies is most likely because patient and control classification was heterogeneous by gender and age, many studies had small samples, and methods of measuring bone mineral density or fractures varied.

    “The lack of consistency in several studies is most likely because the classification of patients and controls was heterogeneous by gender and age, many studies had relatively small samples, and there were many different methods of measuring primary outcomes, such as BMD or fractures.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Young female cancer survivors were significantly more interested in health promotion, such as healthy eating, exercise, and smoking cessation.

    “According to a previous study, young female cancer survivors were significantly more interested in health promotion, such as healthy eating, exercise, and smoking cessation (51).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Demark-Wahnefried, 2000, Current health behaviors and readiness to pursue life-style changes among men and women diagnosed with early stage prostate and breast carcinomas, Cancer. source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    The effect of healthy behaviors of premenopausal women diagnosed with DTC at a relatively young age, such as healthy diet and increased physical activity, might have influenced the increase in BMD.

    “Another possible explanation for our results may be that the effect of healthy behaviors of premenopausal women diagnosed with DTC at a relatively young age, such as healthy diet and increased physical activity, might have influenced the increase in BMD.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The exact TSH levels could not be determined; therefore, no further analyses were performed based on the level of TSH suppression.

    “Fourth, the exact TSH levels could not be determined; therefore, no further analyses were performed based on the level of TSH suppression.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Only studies with a clear control selection were used in the analysis to reduce bias.

    “In addition, only studies with a clear control selection were used in the analysis to reduce bias.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The effects of other confounding factors such as physical activity could not be considered.

    “the effects of other confounding factors such as physical activity could not be considered.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In one meta-analysis, endogenous subclinical hyperthyroidism increased the risk of osteoporotic fractures by 78%, whereas exogenous TSH suppression did not show a high risk of bone deterioration.

    “In 1 meta-analysis, endogenous subclinical hyperthyroidism increased the risk of osteoporotic fractures by 78%, whereas exogenous TSH suppression did not show a high risk of bone deterioration (40).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Yan, 2016, Relationship between subclinical thyroid dysfunction and the risk of fracture: a meta-analysis of prospective cohort studies, Osteoporos Int. source

  • May combine two claims.

    Interpretationcitation

    A meta-analysis by Yoon et al showed a decrease in lumbar and hip bone mineral density in postmenopausal women, and this meta-analysis found a similar result despite including additional studies.

    “A meta-analysis of DTC patients performed by Yoon et al showed a decrease in lumbar and hip BMD in postmenopausal women, and our meta-analysis resulted in a similar finding despite the additional 5 studies that were not included in the previous analysis (9,28,(34)(35)(36).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (9,28,(34)(35)(36)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • Rests on an assumption: The observed associations between TSH suppression therapy and bone mineral density reflect a causal effect of TSH suppression rather than residual confounding.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Postsurgical hypoparathyroidism might attenuate high bone turnover resulting in BMD gain in postmenopausal women.

    “Several studies have reported that postsurgical hypoparathyroidism might attenuate high bone turnover resulting in BMD gain in postmenopausal women (56,57).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [56] Takamura, 2013, Attenuation of postmenopausal bone loss in patients with transient hypoparathyroidism after total thyroidectomy, World J Surg. source
    • cites [57] Fujiyama, 1995, Attenuation of postmenopausal high turnover bone loss in patients with hypoparathyroidism, J Clin Endocrinol Metab. source

  • May combine two claims.

    Study design and conductreasoning

    DXA provides more objective numerical data than fracture investigation, and can reduce the bias caused by compounding factors when collecting data.

    “Given that this method provides more objective numerical data than fracture investigation, it can reduce the bias caused by compounding factors when collecting data.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    Only relatively small sample-sized studies and literature written in English were included.

    “Second, only relatively small sample-sized studies and literature written in English were included.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationown data

    This study could be used to define high-risk groups when determining further treatment policies because this meta-analysis identifies and analyzes sex and menopausal status.

    “However, this study could be used to define high-risk groups when determining further treatment policies because this meta-analysis identifies and analyzes sex and menopausal status.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Our meta-analysis excluded studies that included patients with postsurgical hypoparathyroidism or studies in which the described hypoparathyroidism was ambiguous.

    “In this respect, our meta-analysis excluded studies that included patients with postsurgical hypoparathyroidism or studies in which the described hypoparathyroidism was ambiguous.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Endogenous hyperthyroidism increases osteoclastic bone resorption and decreases osteoblastic bone formation.

    “Especially, endogenous hyperthyroidism increases osteoclastic bone resorption and decreases osteoblastic bone formation (38).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Bassett, 2003, The molecular actions of thyroid hormone in bone, Trends Endocrinol Metab. source

  • May combine two claims.

    Study design and conductnone given

    This meta-analysis included only BMD data taken with DXA equipment, the gold standard diagnostic tool for osteoporosis, including the most recently reported research results.

    “This meta-analysis included only the BMD data taken with the DXA equipment, the gold standard diagnostic tool for osteoporosis, including the most recently reported research results.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    One randomized controlled study found in the comprehensive literature search was not included because it lacked the number for meta-analysis.

    “First, in the comprehensive literature search, 1 randomized controlled study was found, but was not included because it lacked the number for meta-analysis.”
    Quote in the paperNot a substantial claim
32 of 32

  • The paper relies on this without support.

    Healthy controls are an appropriate and comparable comparator to differentiated thyroid cancer patients after thyroidectomy for isolating the effect of TSH suppression therapy on bone mineral density.

    “Eligible studies included prospective or retrospective cohort studies and cross-sectional case-control studies investigating the association between postthyroidectomy TSH suppression therapy and BMD in patients with DTC compared with healthy controls.”
    “ineligible comparators who were not healthy controls, such as”

  • The paper relies on this without support.

    Bone mineral density values measured by dual-energy X-ray absorptiometry across included studies are comparable and can be pooled.

    “the use of BMD measurement methods other than dual-energy X-ray absorptiometry (DXA)”
    “The outcome variables of interest were the mean BMD (g/cm 2 ) in the lumbar spine (LS), FN, or total hip (TH) in comparisons between the TSH suppression group and the control.”

  • The paper relies on this without support.

    The observed associations between TSH suppression therapy and bone mineral density reflect a causal effect of TSH suppression rather than residual confounding.

    “Evidence from observational studies suggests that postmenopausal women treated with TSH suppression therapy are at risk for lower BMD.”
    “Therefore, to date, the risk of decreased BMD from TSH suppression therapy after thyroidectomy in postmenopausal women with DTC could be acceptable as a concordant result.”

  • The paper relies on this without support.

    The duration of TSH suppression therapy reported in included studies is accurate and comparable enough for subgroup analysis.

    “The duration of TSH inhibition varied from 1 to 15 years, and in postmenopausal women, the mean BMD difference between the TSH suppression group and the control group was slightly correlated according to the TSH inhibition period.”
    “we performed subgroup analyses of BMD at each site according to the duration of TSH suppression therapy: ≤5 years and >5 years.”

  • The paper relies on this without support.

    The three studies excluded from meta-analysis because they lacked sex- and menopausal-status-specific bone mineral density values do not systematically differ from included studies.

    “3 studies that did not provide specific BMD values according to the subjects' sex and menopausal status were used only for a systematic review of the literature (22)(23)(24).”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Overtreatment of LT4 is associated with adverse effects on bone.

    “And overtreatment of LT4 is associated with adverse effects on bone [14, 15].”

    From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [15]

    The Discussion reports that postoperative TSH suppression therapy with levothyroxine was associated with reduced lumbar-spine and total-hip bone mineral density in postmenopausal women with differentiated thyroid cancer. The claim generalizes this adverse bone effect beyond that group; the Discussion also says the effect of TSH suppression therapy on osteoporosis remains unclear. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Postmenopausal women with thyroid cancer receiving TSH suppression therapy may have a risk for lower BMD compared with those who did not.

    “Similarly, the results of a meta-analysis [15] involving 1824 participants showed that postmenopausal women with thyroid cancer receiving TSH suppression therapy may have a risk for lower BMD compared with those who did not.”

    From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [15]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Lumbar-spine subgroup counts exceed the reported meta-analysis totals

    Minor

    The lumbar-spine groups are separated by menopausal status and sex, but their patient counts sum to 767, exceeding the reported 739 patients. Their control counts also sum to 1,113, exceeding the reported 1,085 controls.

    Reported 739 · recomputed 767

1 of 1

Cites

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Related

Authors
Ku, E. J., Yoo, W. S., Lee, E. K., Ahn, H. Y., Woo, S. H., Hong, J. H., Chung, H. K., & Park, J.-W.
Affiliations
  • Chungbuk National University (KR)
  • Dankook University Hospital (KR)
  • National Cancer Center (KR)
  • Chung-Ang University (KR)
  • Daejeon Eulji Medical Center, Eulji University (KR)
Corresponding author
Park, Jin-Woo
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2021-07-24
Volume
106
Issue
12
Pages
3655-3667
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/clinem/dgab539
OpenAlex
W3183969154
Semantic Scholar
fbc29af1134ba9976b2c4417558c93b9a9c7873b
Cited by
57
References
57
Citations by year
2026: 6 · 2025: 18 · 2024: 15 · 2023: 10 · 2022: 5 · 2021: 3
FWCI
1.96
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
  • Figshare (cc-by)
Funders
Ministry of Health & Welfare, Republic of Korea (HC19C0103040020)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Keywords
TSH suppression therapy, bone mineral density, differentiated thyroid cancer, subclinical hyperthyroidism, osteoporosis, total thyroidectomy, postmenopausal women, premenopausal women, lumbar spine, femoral neck, total hip
MeSH terms
Adenocarcinoma, Humans, Hyperthyroidism, Osteoporosis, Prognosis, Thyroid Neoplasms, Thyroidectomy, Thyrotropin, Bone Density

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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