Bisphosphonates in the Treatment of Thalassemia-Induced Osteoporosis

Abstract

The aim of our randomized, placebo-controlled study was to investigate the effects of 2 years' daily oral administration of alendronate or intramuscular administration of clodronate every 10 days, on bone remodeling parameters and bone mineral density (BMD), safety and tolerability in a group of osteoporotic thalassemic patients. Twenty-five young patients (mean age 26.6 +/- 7.1 years) with beta-thalassemia major were randomly divided to receive placebo or 100 mg of clodronate intramuscularly every 10 days or 10 mg of alendronate per os daily. All patients took 500 mg of elemental calcium and 400 IU cholecalciferol in the evening at meal time. After 2 years, pyridinium crosslinks, which are bone resorption markers, did not differ significantly from baseline values in the placebo group, whereas they had decreased significantly in the clodronate and alendronate groups. Osteocalcin, a bone formation marker, did not change significantly in the placebo group, whereas it decreased slightly, but not significantly, in the clodronate and alendronate groups after 12 and 24 months. At the end of the study, the lumbar spine BMD had decreased significantly in the placebo group; it did not change significantly in the clodronate group; in the alendronate group it had increased but not significantly, whereas the increase was significant with respect to the placebo group. Femoral neck BMD decreased significantly in the placebo group; it did not change significantly in the clodronate group, but increased significantly in the alendronate group. No relevant side effects were recorded during our study. In conclusion, in patients with thalassemia-induced osteoporosis, the daily administration of alendronate significantly increases BMD, the most important predictor of the risk of fracture at several sites. Clodronate treatment at our dosage is ineffective in this pathology in spite of the good compliance of patients.

Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis

“…However, despite improved treatment for this hematologic disorder and its complications, TM patients exhibit unbalanced bone turnover, with increased bone resorption and decreased bone formation resulting in diminished bone mineral density (BMD) [7][8][9][10]. The RANK/RANK-L/OPG system has been recognized as a major regulator of osteoclast proliferation and activation, and its role has also been described in the pathogenesis of TM-induced osteoporosis Abstract Subjects affected by thalassemia major (TM) often have reduced bone mass and increased fracture risk.…”

Anabolic therapy in b-thalassaemia major induced osteoporosis: case report and literature review

“…Una bassa DMO è associata, nei T, alla cardiomiopatia, al diabete, all'epatite cronica, all'incremento delle transaminasi, all'amenorrea (31) ed alla mancata terapia ormonale sostitutiva nei casi di ipogonadismo ipogonadotropo (29)(30)(31). A carico del tessuto osseo, in corso di ST si determina: -basso valore del rapporto osteoprotegerina (OPG)/ RANKL con (a) livelli di OPG sovrapponibili (39) o diminuiti (40,41) e (b) netto aumento del RANKL rispetto alla popolazione generale (39); -alti livelli di cross-links del piridinio e di N-telopeptidi urinari (39,(41)(42)(43); -livelli diminuiti di osteocalcina, fosfatasi alcalina ossea e C telopeptide del procollagene I (40, 43); -riduzione della attività osteoblastica a causa dei depositi di ferro (44); -ridotta 25-idrossilazione della vitamina D a causa della emosiderosi epatica e della possibile presenza di epatite post-trasfusionale (33, 34); -ridotta secrezione di GH con conseguente ridotta proliferazione degli OB (9, 45) e, da parte di questi ultimi, ridotta secrezione di insulinlike growth factor I (IGF-I) (39) e di Insulin-like growth factor binding protein-3 (IGFBP-3) (29); -correlazione statisticamente significativa dei diminuiti livelli di IGF-I con la diminuizione della DMO (41); -correlazione inversa tra l'aumento del RANKL ed i livelli di testosterone libero e 17-b-estradiolo (39).…”

Evaluation of bone mineral density in patients with hemoglobin H disease

“…Additional studies found that osteopenia and osteoporosis are emerging as important causes of morbidity in patients of both genders with thalassemia [14,19,[23][24][25].…”