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Modificazioni omeostatiche del Fibroblast Growth Factor 23 in pazienti con Emocromatosi primitiva sottoposti a whole blood donation e valutazione della loro salute scheletrica
Full text linkBackground: Il tessuto scheletrico è in grado di secernere diverse sostanze ormonali rilevanti per l’organismo.
Negli ultimi anni è stata posta una particolare attenzione nei confronti di un ormone secreto prevalentemente dagli osteociti, denominato Fibroblast growth factor 23 (FGF23). L’FGF23 regola il metabolismo dei fosfati (azione fosfaturica) e del sistema della vitamina D (inibizione della conversione in prodotti attivi). La secrezione di questa sostanza è regolata anche da “meccanismi non scheletrici”, tra i principali, l’assetto marziale, la flogosi e l’anemia.
Obiettivo: Valutare l’FGF23 in un modello in vivo rappresentato dall’Emocromatosi Primitiva (HE) in condizioni basali e dopo la procedura di donazione di sangue intero (whole blood donation).
Materiali e Metodi: Sono stati arruolati n= 26 soggetti affetti da HE e n= 19 donatori sani. FGF23 è stato valutato con entrambe le metodiche disponibili in commercio, ovvero misurando sia la componete intatta e biologicamente attiva (iFGF23), che la porzione C-terminale (cFGF23).
In aggiunta è stata effettuata una valutazione dell’assetto marziale completo, del metabolismo minerale e scheletrico comprensivo anche della misurazione della densità minerale scheletrica (BMD) e del rilievo di deformità vertebrali. La popolazione oggetto dello studio è stata confrontata con donatori volontari sani (C).
Risultati: Non sono state rilevate differenze significative in merito al metabolismo calcio fosforico al baseline e dopo rivalutazione.
Per quanto concerne l’analisi di FGF23, non abbiamo riscontrato differenze dei livelli della porzione intatta tra i due gruppi al basale (HE0: iFGF23 54.27 ± 14.42 pg/mL vs C0: iFGF23 52.77 ± 17.63 pg/mL), né dopo la donazione (HE1: iFGF23 54.70 ± 15.48 pg/mL vs C1: iFGF23 53.20 ± 15.88 pg/mL).
Invece è stata riscontrata una differenza nei livelli circolanti di cFGF23, che correlava in maniera significativa con i parametri dell’assetto marziale dopo la procedura di donazione (p <0,001).
Il rapporto tra la porzione intatta e la porzione C-terminale (iFGF23/cFGF23 ratio) è rimasto costante, mentre i parametri dell’assetto marziale come atteso si riducevano dopo la whole blood donation.
Dalla valutazione densitometrica è emersa una lieve riduzione della BMD nel gruppo HE (p = ns).
Mediante valutazione morfometrica è stato rilevato il 20% di fratture vertebrali nel gruppo HE rispetto al 5% del gruppo di controllo (p= ns).
Conclusioni: Questo è il primo studio in cui è stato valutato l’FGF23 nell’ HE.
La valutazione di entrambe le componenti dell’FGF23 (intatta e C-terminale), unitamente all’assetto marziale ed alle sue variazioni dopo la procedura di whole blood donation, ha consentito di valutare il comportamento biologico di questo ormone al fine di incrementare le conoscenze nel campo dell’omeostasi dei fosfati. I dati rilevati consentono di affermare che l’FGF23 è influenzato dall’assetto marziale e come questo eserciti un feedback sulla degradazione di FGF23, al fine di mantenere l’omeostasi dei fosfati e di prevenire la demineralizzazione scheletrica. In aggiunta è stato effettuato un assessment della compromissione scheletrica in una popolazione affetta da HE più giovane rispetto a quella analizzata finora in letteratura
At the intersection between skeletal and hematopoietic systems. incorporating hemoglobin in FRAX®
No full textUnderstanding and managing secondary osteoporosis
No full textIntroduction: The term secondary osteoporosis (SO) identifies a reduction of bone mass related to a well-established disease or pharmacological agent. The identification of the underlying disease often represents a challenging situation in clinical practice. Areas covered: The prevalence of SO in the real world may vary, ranging from 17% to 80%; therefore, search for a form of SO represents a pillar when evaluating patients with osteoporosis. Guidelines for treatment of specific secondary forms of osteoporosis, such as glucocorticoid-induced osteoporosis, have been published even though often neglected in clinical practice. For the majority of SO, there are currently no specific guidelines concerning treatment with only few trials showing the effect of bone-active drugs on fracture risk reduction. Expert opinion: Healthcare professionals should be aware of the secondary forms of osteoporosis, in particular when the reason for reduced skeletal resistance is uncertain or when bone mineral density results are unsatisfactory in a patient compliant to therapy. In a few cases (such as, for example: no response to therapy, better classification of bone involvement in patients with kidney failure, suspicion of rare metabolic bone disease) bone biopsy is needed to investigate the patient. This review highlights recent advances in understanding and managing SO
Bone loss after discontinuation of denosumab. the devil is in the details
No full textA 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications
Appropriate dosing of burosumab in tumor-induced osteomalacia
No full textWe appreciated the recently published paper of Crotti and coworkers in which the authors reported a patient with tumor-induced osteomalacia (TIO) treated with burosumab for over 2 years for a tumor located in the pre-sacral region that recurred 18 months after excision. Recurrence was associated with decline of serum phosphate (SP) and increase of serum FGF23. After 4 years of treatment with calcitriol and phosphorus supplements without SP normalization, burosumab was started “at the dose of 0.3 mg/kg/month.” The starting dose of burosumab used in this patient was the same used in two previous trials on TIO adult patients. However, in these studies, the overall effects were not completely satisfactory
Vitamin D and secondary hyperparathyroid states
No full textThe interplay between Vitamin D and parathyroid hormone (PTH) represents one of the most important metabolic mechanisms of regulation of the calcium/phosphorus homeostasis. Secondary hyperparathyroidism is therefore a major complication that arises as a result of reduced Vitamin D levels, both as primary 25-hydroxy-vitamin D (25[OH]D) and/or 1,25-dihydroxyvitamin D (1,25[OH]2D) reduction. Different metabolic pathways are involved, as well as target organs and tissues, with several clinical complications. The skeleton is primarily involved, but many other extra-skeletal organs expressing the Vitamin D and/or PTH receptors may theoretically be affected by Vitamin D inadequacy and secondary hyperparathyroidism. Mechanisms associated with low Vitamin D (mostly, but not exclusively 1,25[OH]2D deficiency) and high serum PTH also intensify chronic kidney disease (CKD), with further consequences on the mineral metabolism system and development of skeletal and cardiovascular disease. Therapeutic intervention is primarily aimed at enhancing serum 25(OH)D levels and reducing secondary hyperparathyroidism, by employing different strategies and endpoints according to the clinical contest. This chapter reviews the current knowledge on the metabolic pathways involved in the Vitamin D/PTH axis regulation in different clinical settings and gives an update on the recommended treatment strategies
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