Background: Survivors of pediatric differentiated thyroid carcinoma (DTC) receive thyrotropin-suppressive therapy to minimize disease recurrence. However, knowledge about long-term effects of... Show moreBackground: Survivors of pediatric differentiated thyroid carcinoma (DTC) receive thyrotropin-suppressive therapy to minimize disease recurrence. However, knowledge about long-term effects of subclinical hyperthyroidism on bone mineral density (BMD) in pediatric DTC survivors is scarce, as is the information regarding long-term consequences of permanent hypoparathyroidism on BMD. We evaluated BMD in pediatric DTC survivors and investigated if BMD was affected by subclinical hyperthyroidism and/or permanent hypoparathyroidism during long-term follow-up.Methods: In this nationwide longitudinal study, we determined BMD in the lumbar spine and femur by dual energy X-ray absorptiometry in 65 pediatric DTC survivors. Measurements were repeated after minimal 5 years of follow-up in 46 pediatric DTC survivors. BMD results were evaluated according to the recommendations of the International Society for Clinical Densitometry (ISCD) and WHO. At both visits, we determined biochemical parameters and markers of bone resorption (C-terminal telopeptide of type I collagen [beta-CTX]) and formation (N-propeptide of type I collagen [PINP] and osteocalcin).Results: First and second BMD measurements were done after a median follow-up of 17.0 (interquartile range [IQR] 8.0-25.0) and 23.5 (IQR 14.0-30.0) years after diagnosis, respectively. Median age at diagnosis was 15 years (IQR 13.0-17.0). Twenty-nine percent of the survivors had subclinical hyperthyroidism. In most survivors, BMD T- and Z-scores were within the reference range during both BMD evaluations. However, after 23.5 years of follow-up, a low BMD was found in 13.0%. In the 13 survivors with permanent hypoparathyroidism, BMD values did not differ after 5 years of follow-up compared with baseline values or in comparison with the 33 survivors without permanent hypoparathyroidism. During follow-up, turnover markers beta-CTX and PINP remained stable.Conclusions: This longitudinal study of pediatric DTC survivors demonstrated normal and stable median lumbar spine and femur BMD values after a median time of 17 and 23.5 years after diagnosis. However, compared with controls, a lower BMD was still found in 13.0% after prolonged follow-up despite intensive follow-up. Based on the studied follow-up period, these data do not provide convincing evidence in support of standard monitoring of bone mass among DTC survivors, but may be restricted to individual cases at low frequency. Show less
Makras, P.; Appelman-Dijkstra, N.M.; Papapoulos, S.E.; Wissen, S. van; Winter, E.M.; Polyzos, S.A.; ... ; Anastasilakis, A.D. 2021
Context: Zoledronate is used to prevent bone loss following denosumab discontinuation but its efficacy differs among studies.Objective: To test if the duration of denosumab treatment affects the... Show moreContext: Zoledronate is used to prevent bone loss following denosumab discontinuation but its efficacy differs among studies.Objective: To test if the duration of denosumab treatment affects the efficacy of subsequent zoledronate infusion.Methods: This multicenter, prospective cohort study, conducted at 2 Greek and 1 Dutch bone centers, included 47 postmenopausal women (n=47) who received a single zoledronate infusion 6 months after the last denosumab injection and then were followed for 1 year. Twenty-seven women received <= 6 denosumab injections (<= 6 Group) and 20 received>6 denosumab injections (> 6 Group). The main outcome measure was changes in lumbar spine (LS) bone mineral density (BMD).Results: At 12 months LS-BMD values were maintained in the <= 6 Group (0.980.10 to 0.99 +/- 0.9 g/cm(2), P=0.409) but decreased significantly in the>6 Group (1.0 +/- 0.11 to 0.93 +/- 0.12 g/cm(2), P<0.001). The percent change of LS-BMD of the <= 6 Group (+1.0%) was significantly different (P<0.001) from the change of the>6 Group (-7.0%). In the whole cohort, the duration of denosumab treatment was negatively correlated with the percentage change of LS-BMD (r(s) = -0.669, P<0.001) but not with the change of femoral neck (FN)-BMD. Bone turnover markers increased in all patients 6 months following zoledronate administration with no difference between the 2 groups.Conclusion: The duration of denosumab treatment significantly affects the efficacy of subsequent zoledronate infusion to maintain BMD gains. Frequent follow-up of patients treated with denosumab longer than 3 years is advisable as additional therapeutic interventions may be needed. Show less
Santen, S.S. van; Olsson, D.S.; Hammarstrand, C.; Wijnen, M.; Fiocco, M.; Heuvel-Eibrink, M.M. van den; ... ; Neggers, S.J.C.M.M. 2020
Context: Patients with craniopharyngioma suffer from obesity and impaired bone health. Little is known about longitudinal changes in body composition and bone mineral density (BMD).Objective: To... Show moreContext: Patients with craniopharyngioma suffer from obesity and impaired bone health. Little is known about longitudinal changes in body composition and bone mineral density (BMD).Objective: To describe body composition and BMD (change).Design: Retrospective longitudinal study.Setting: Two Dutch/Swedish referral centers.Patients: Patients with craniopharyngioma (n = 112) with a dual X-ray absorptiometry (DXA) scan available (2 DXA scans, n = 86; median time 10.0 years; range 0.4-23.3) at age >= 18 years (58 [52%1 male, 50 [45%] childhood onset).Main outcome measures: Longitudinal changes of body composition and BMD, and associated factors of Delta Z-score (sex and age standardized).Results: BMI (from 28.8 +/- 4.9 to 31.2 +/- 5.1 kg/m(2), P< .001), fat mass index (FMI) (from 10.5 +/- 3.6 to 11.9 +/- 3.8 kg/m(2), P= .001), and fat free mass index (FFMI) (from 18.3 +/- 3.2 to 19.1 +/- 3.2 kg/m(2) , P< .001) were high at baseline and increased. Fat percentage and Z-scores of body composition did not increase, except for FFMI Z-scores (from 0.26 +/- 1.62 to 1.06 +/- 2.22, P< .001). Z-scores of total body, L2-L4, femur neck increased (mean difference 0.61 +/- 1.12, P< .001; 0.74 +/- 1.73, P< .001; 0.51 +/- 1.85, P= .02). Linear regression models for AZ-score were positively associated with growth hormone replacement therapy (GHRT) (femur neck: beta 1.45 [95% CI 0.51-2.39]); and negatively with radiotherapy (femur neck: beta -0.79 [-1.49 to -0.09]), glucocorticoid dose (total body: beta -0.06 (-0.09 to -0.02]), and medication to improve BMD (L2-L4: beta -1.06 [-1.84 to -0.28]).Conclusions: Z-scores of BMI, fat percentage, and FMI remained stable in patients with craniopharyngioma over time, while Z-scores of FFMI and BMD increased. Higher glucocorticoid dose and radiotherapy were associated with BMD loss and GHRT with increase. Show less
The current gold standard for the diagnosis of osteoporosis and the prediction of fracture risk is the measurement of bone mineral density (BMD) using dual energy x-ray absorptiometry (DXA). A low... Show moreThe current gold standard for the diagnosis of osteoporosis and the prediction of fracture risk is the measurement of bone mineral density (BMD) using dual energy x-ray absorptiometry (DXA). A low BMD is clearly associated with increased fracture risk, but BMD is not the only determinant of bone strength, particularly in secondary osteoporosis and metabolic bone disorders in which components other than BMD are affected and DXA often underestimates true fracture risk. Material properties of bone which significantly contribute to bone strength have become evaluable in vivo with the impact microindentation (IMI) technique using the OsteoProbe (R) device. The question arises whether this new tool is of added value in the evaluation of bone fragility. To this effect, we conducted a systematic review of all clinical studies using IMI in vivo in humans also addressing practical aspects of the technique and differences in study design, which may impact outcome. Search data generated 38 studies showing that IMI can identify patients with primary osteoporosis and fractures, patients with secondary osteoporosis due to various underlying systemic disorders, and scarce longitudinal data also show that this tool can detect changes in bone material strength index (BMSi), following bone-modifying therapy including use of corticosteroids. However, this main outcome parameter was not always concordant between studies. This systematic review also identified a number of factors that impact on BMSi outcome. These include subject- and disease-related factors such as the relationship between BMSi and age, geographical region and the presence of fractures, and technique- and operator-related factors. Taken together, findings from this systematic review confirm the added value of IMI for the evaluation and follow-up of elements of bone fragility, particularly in secondary osteoporosis. Notwithstanding, the high variability of BMSi outcome between studies calls for age-dependent reference values, and for the harmonization of study protocols. Prospective multicenter trials using standard operating procedures are required to establish the value of IMI in the prediction of future fracture risk, before this technique is introduced in routine clinical practice. Show less
Hellemond, I.E.G. van; Smorenburg, C.H.; Peer, P.G.M.; Swinkels, A.C.P.; Seynaeve, C.M.; Sangen, M.J.C. van der; ... ; Dutch Breast Canc Res Grp BOOG 2019
The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2-3 years of tamoxifen. This planned... Show moreThe phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2-3 years of tamoxifen. This planned side-study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate-use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T-scores we used linear mixed models with random patients effects. Of 1860 eligible DATA patients, 910 (48.9%) had a baseline BMD measurement. Among patients with a normal baseline BMD (n = 417), osteopenia was observed in 53.5% and 55.4% in the 6- and 3-year group respectively (p = 0.18), during follow-up. Only two patients (3-year group) developed osteoporosis. Of the patients with osteopenia at baseline (n = 408), 24.4% and 20.4% developed osteoporosis respectively (p = 0.89). Three years after randomisation 18.3% and 18.2% used bisphosphonates in the 6- and 3-year groups respectively and 6 years after randomisation this was 23.7% and 20.9% respectively (p = 0.90) of which the majority used oral bisphosphonates. The yearly mean BMD-change during anastrozole in the lumbar spine showed a T-score decline of 0.075. After bisphosphonate addition the decline became less prominent (0.047 (p < 0.001)) and after anastrozole cessation, while continuing bisphosphonates, the mean BMD yearly increased (0.047 (p < 0.001)). In conclusion, extended anastrozole therapy was not associated with a higher incidence of osteoporosis. Anastrozole-use was associated with a BMD decrease; however, the decline was modest and partially reversible after anastrozole cessation. Show less
