Comparison of Bone Mineral Density and Trabecular Bone Score in Patients with and without Vertebral Fractures and Differentiated Thyroid Cancer with Long-Term Serum Thyrotrophin-Suppressed Therapy.

INTRODUCTION: The study of BMD provides only partial information on bone health in patients undergoing TSH suppression therapy due to differentiated thyroid cancer (DTC). The trabecular bone score (TBS), a new parameter assessing bone microarchitecture, is proposed for studying bone in this context. This study aimed to analyze their long-term use in patients with DTC. METHODS: Bone mineral density (BMD) was measured by dual X-ray densitometry (DXA) and TBS was assessed with iNsigth software (version 2.0, MediImaps, France) in 145 postmenopausal patients with DTC. Vertebral fractures (VFs) were identified using a semi-quantitative X-ray method. RESULTS: The BMD at the end of this study did not differ from the initial measurement. However, the TBS decreased from 1.35 ± 0.1 to 1.27 ± 0.1 (p = 0.002). Increased levels of PTH, osteocalcin, and bone alkaline phosphatase (BAP) were observed, suggesting enhanced bone remodeling. There was an increase in the prevalence of osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%, respectively). The proportion of patients with partially degraded and totally degraded TBS increased from 31% and 15.1% to 48.9% and 24.8% by the end of this study. Among the 30 patients with VFs, there were no significant differences in age, body mass index (BMI), calcium intake, alcohol consumption, smoking, radioiodine, therapy, or thyroid parameters compared to those without VFs. The odds ratio for VFs increased with osteopenia (OR 2.63). Combining TBS with BMD did not improve discrimination. CONCLUSIONS: The TBS decreased while the BMD remained unchanged. The percentage of patients with osteoporosis and osteopenia, whether partially degraded or totally degraded, increased by the end of this study. The predominant discordance was found in partially degraded microarchitectures, with a higher proportion of osteopenic patients compared to those with normal or osteoporotic bone density. The AUC of the combination of TBS and BMD did not enhance discrimination. TBS, radioactive iodine therapy, and sedentary lifestyle emerged as the main distinguishing factors for DTC patients with VFs.

Bone loss induced by cancer treatments in breast and prostate cancer patients.

Cancer and cancer therapies are a major factor risk for osteoporosis due to bone loss and deterioration of bone microarchitecture. Both factors contribute to a decrease in bone strength and, consequently, increased bone fragility and risk of fracture. Cancer-associated bone loss is a multifactorial process, and optimal interdisciplinary management of skeletal health, accurate assessment of bone density, and early diagnosis are essential when making decisions aimed at reducing bone loss and fracture risk in patients who have received or are receiving treatment for cancer. In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific society SEOM. The aim was to provide an up-to-date and in-depth view of osteoporotic risk and its consequences, and to present a series of recommendations aimed at optimizing the management of bone health in the context of cancer.

Trabecular bone score and bone mineral density in patients with long-term controlled acromegaly.

OBJECTIVE: Acromegaly is associated with increased vertebral fracture (VFs) risk not correlated to bone mineral density (BMD). Trabecular bone score (TBS), related to bone microarchitecture, provides information on bone strength. This cross-sectional study considered the usefulness of TBS and BMD to assess bone status in long-term controlled acromegalic patients. DESIGN, PATIENTS, MEASUREMENTS: 26 acromegaly patients (14 female and 12 males) were included in the study. A further 117 subjects were recruited as controls (58 females and 57 males). BMD was measured using dual-energy X-ray absorptiometry (DXA), TBS was obtained applying Medimaps software 2.0. Biochemical parameters were determined by standardized techniques. RESULTS: 73% of patients with acromegaly exhibited normal lumbar spine (LS) BMD. TBS was normal in 38% of acromegalic patients and partially degraded or degraded in 31% of patients, respectively. No differences were found in LS BMD between acromegalic patients and controls. TBS values were significantly lower in patients with acromegaly (1.27 ± 0.13 vs. 1.35 ± 0.17, p = .01). Postsurgical remission was associated with higher TBS values (1.35 ± 0.10 vs. 1.23 ± 0.13, p = .02) and pituitary radiotherapy treatment with lower TBS values (1.18 ± 0.12 vs. 1.31 ± 0.12, p = .004). On multivariate analysis, age, BMI and LS BMD were predictors of TBS changes in patients with acromegaly (p < .05). CONCLUSIONS: Patients with long-term controlled acromegaly can exhibit deterioration of bone microstructure measured with TBS, despite BMD measurement not showing bone loss. Our study suggests that TBS is useful for monitoring the bone status changes in acromegalic patients.

Association of Low Serum 25OHD Levels with Abnormal Bone Microarchitecture in Well-Differentiated Thyroid Cancer.

The association of low levels of 25 hydroxyvitamin D (25OHD) with papillary thyroid cancer (PTC) is being studied, as to whether it is a risk factor or as a coincidental one. This study aimed to evaluate serum levels of deficiency, insufficiency, and sufficiency of 25OHD in PTC and its relationship with the trabecular bone score (TBS) and bone mineral density (BMD). This study includes 134 postmenopausal women with PTC, followed for 10 years. BMD was measured with DXA Hologic QDR 4500, and TBS with Med-Imaps iNsight2.0 Software. Mean serum 25OHD was 23.09 ± 7.9 ng/mL and deficiency, insufficiency, and sufficiency levels were 15.64 ± 2.9, 25.27 ± 2.7, and 34.7 ng/mL, respectively. Parathyroid hormone (PTH) and bone alkaline phosphatase (BAP) were higher in deficiency (57.65 ± 22.6 ng/mL; 29.5 ± 14 U/L) and in insufficiency (45.88 ± 19.8 ng/mL; 23.47 ± 8.8 U/L) compared with sufficiency of 25OHD (47.13 ± 16 and 22.14± 9.7 ng/mL) (p = 0.062 and p = 0.0440, respectively). TBS was lower in patients with 25OHD < 20 ng/mL (1.24 ± 0.13) compared with between 20-29 (1.27 ± 0.13, p < 0.05) and 30 ng/mL (1.31 ± 0.11, p < 0.01). We found low TBS in patients with PTC and long-term follow-up associated with low serum 25OHD levels, not associated with cancer stage, or accumulative iodine radioactive dose. Low 25OHD associated with deleterious bone quality in patients with PTC should be restored for the prevention of fractures.

Trabecular bone deterioration in differentiated thyroid cancer: Impact of long-term TSH suppressive therapy.

BACKGROUND: Conflicting results has been reported regard osteoporosis and fractures in patients with Differentiated Thyroid Cancer (DTC). Our objective was to evaluate the long-term effects of TSH suppression therapy with Levothyroxine (LT4) on trabecular bone score (TBS) and bone mineral density (BMD) in females with DTC after thyroidectomy. METHODS: About 145 women with resected DTC and receiving long-term TSH therapy, were stratified according to the degree of TSH suppression. Mean duration of follow-up was 12.3 ± 6.1 years. BMD and TBS, were assessed using dual-energy X-ray absorptiometry (DXA) and TBS iNsight (Med-Imaps), at baseline (1-3 months after surgery) and at the final study visit. RESULTS: In patients stratified by duration of TSH suppression therapy (Group I, 5-10 years; Group II, >10 years), slight increases from baseline TSH levels were observed. Significant decreases in LS-BMD and FN-BMD were seen in patients after >10 years. TBS values were lower in Groups I (1.289 ± 0.122) and II (1.259 ± 0.129) compared with baseline values (P = .0001, both groups). Regarding the degree of TSH suppression, TBS was significantly reduced in those with TSH < 0.1 µU/mL (P = .0086), and not in patients with TSH suppression of 0.1.-0.5 or >0.5 µU/mL. CONCLUSIONS: We found deterioration of trabecular structure in patients with DTC and TSH suppression therapy below 0.1 µU/mL and after 5-10 years of follow-up. Significant changes in BMD according to TSH levels were not observed. Trabecular Bone Score is a useful technique for identifying thyroid cancer patients with risk of bone deterioration.

Hypophosphataemic Rickets: Similar Phenotype of Different Diseases.

Hypophosphataemic rickets (HR) is a group of rare disorders caused by excessive renal phosphate wasting in which the participation of fibroblast growth factor 23 (FGF23) can be prominent. These diseases pose therapeutic challenges with important consequences for growth and bone development in childhood, with higher risk of fractures and poorer bone healing, dental problems, and nephrolithiasis or nephrocalcinosis. In some cases, the diagnostic delay can be very long; laboratory findings and an exhaustive anamnesis could help distinguish between various pathologies, and FGF23 values-although currently not routinely measured-have implications for the differential diagnosis. Genetic testing is encouraged, especially in sporadic or insidious cases. In this review we discuss the clinical features of HR, with a particular emphasis on the differential diagnosis and the therapeutic implications.

Low trabecular bone score in postmenopausal women with differentiated thyroid carcinoma after long-term TSH suppressive therapy.

The effect of thyroid suppression therapy (TST) on trabecular bone scores (TBS) and bone mineral density (BMD) in thyroidectomized women with differentiated thyroid carcinoma (DTC) on long-term follow-up is presently not conclusive. PATIENTS AND METHODS: We carried out a study in 61 premenopausal and 84 postmenopausal Caucasian women with DTC. Serum biochemistry, bone markers, TBS, BMD, and bone fractures were evaluated 1-3 months post surgery and after a median follow-up of 10 years. RESULTS: In the final study, patients belonged to Group I Premenopausal (n = 14) who remained in this status; Group II Premenopausal who became postmenopausal (n = 47); Group III patients who were and continued as postmenopausal (n = 84). Baseline premenopausal patients had a normal TBS mean value of 1.39 ± 0.14 significantly higher than that found in postmenopausal 1.31 ± 0.12 (p = 001). In the final study, premenopausal patients continued to have a normal TBS of 1.46 ± 0.08 compared to the significantly lower value of postmenopausal patients 1.25 ± 0.11 (p = 0.0009). Lumbar BMD (L-BMD) loss after the long-term study was significant in Group II (0.99 g/cm2 ± 0.13 vs. 0.91 ± 0.12 g/cm2, p < 0.0001) and there was a slight, but not significant, bone loss in Group I (1.00 ± 0.12 vs. 0.98 ± 0.11, p = 0.1936) and in Group III (0.86 ± 0.12 vs. 0.84 ± 0.15, p = 0.1924) compared with baseline values. CONCLUSION: Longer-term suppression therapy in female patients with DTC did not increase significantly the risk of bone loss, although we found in postmenopausal patients deterioration of bone microarchitecture. TBS study should be considered in the evaluation of postmenopausal DTC patients on long-term DTC for the evaluation of the risk of fractures.

Recalcitrant hypocalcaemia in a patient with post-thyroidectomy hypoparathyroidism and Roux-en-Y gastric bypass.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) places patients at an increased risk of hypocalcaemia due to the reduction in calcium absorption (because the procedure bypasses the duodenum and jejunum) and vitamin D deficiency. Subsequent thyroid surgery increases the risk of severe hypocalcaemia due to potential post-operative hypoparathyroidism. Only a few cases have been published before of this type of treatment-challenging hypocalcaemia. CLINICAL PRESENTATION: We report the case of a 31-year-old woman with a previous RYGB, who suffered severe and symptomatic chronic hypocalcaemia after total thyroidectomy. She required aggressive therapy with oral calcium and calcitriol and frequent calcium infusions, but there was no improvement in serum calcium level. Due to the lack of response to standard therapy, teriparatide treatment was started (first with subcutaneous injections and thereafter with a multipulse subcutaneous infusor) but the results were disappointing. As there was no response to different medical treatments, reversal of RYGB was performed with no complications and a subsequent sustained increase in serum calcium level. CONCLUSIONS: This case shows that patients with postoperative hypoparathyroidism and RYGB have increased risk of severe recalcitrant symptomatic hypocalcaemia. In our case teriparatide was ineffective but, as this is the first patient reported, more results are needed to evaluate properly the effect of teriparatide in this multifactorial hypocalcaemia. Reversal of RYGB should be considered when medical therapy has failed, because surgery restores an adequate absorption of calcium and vitamin D from previously bypassed duodenum and proximal jejunum.

[Normocalcemic primary hyperparathyroidism: a growing problem]. / Hiperparatiroidismo primario normocalcémico: un problema en aumento.

Normocalcemic primary hyperparathyroidism is at present one of the most common reasons for consultation in bone metabolism units. It is characterized by increased levels of intact parathyroid hormone in the presence of normal serum calcium (total and ionized) in generally asymptomatic individuals. The differential diagnosis should be considered in all situations that occur with secondary hyperparathyroidism. Its natural history is not well known, and it does not always progress to hypercalcemia. As a recently recognized entity, there are still no specific recommendations for its management. In this review we discuss some aspects of this entity, emphasizing the importance of a proper laboratory diagnosis, assessing possible signs or symptoms associated such as kidney stones or osteoporosis, which can help the clinician to take a conservative or interventionist attitude.

[Concept, etiology and epidemiology of primary hyperparathyroidism]. / Concepto, etiología y epidemiología del hiperparatiroidismo primario.

Primary hyperparathyroidism (PHPT) is one of the most frequent endocrinological disorders. In PHPT, there is abnormal regulation of parathyroid hormone (PTH) by calcium, which translates into inappropriately high PTH secretion for the level of calcemia. Most patients with PHPT have increased serum PTH levels, with increases in serum calcium, especially ionic calcium. The incidence of PHPT rises with age, the mean age at diagnosis being 55 years. This disorder affects mainly women with a female-to-male ratio of approximately 3:1. Most (80-85%) of cases are produced by chief cell parathyroid adenomas. The factors involved in the genesis of PHPT are largely unknown. Gene mutations affecting oncogenes (cyclin D1, RET) or tumor suppressor genes (MEN1, HRPT2) are found in a minority of cases. These mutations are especially important in familial forms of PHPT, such as multiple endocrine neoplasia syndrome (MEN1, MEN2A). No mutations affecting the calcium-sensing receptor (CaSR) or vitamin D receptor (VDR) gene have been found. In parathyroid adenomas and hyperplasias, there may be abnormal Wnt signalling, with mutations of the coreceptor LRP5 gene and beta-catenin accumulation. Expression of the Klotho protein, which intervenes in serum calcium regulation, is reduced. Low levels of 25(OH) vitamin D frequently coexist, although whether vitamin D deficiency plays a pathogenic role in PHPT is unknown.