Effects of Hormonal Replacement Therapy on Bone Metabolism in Young Adults with Beta-thalassemia Major

Lasco, Antonino; Morabito, Nunziata; Gaudio, Agostino; Buemi, Michele; Wasniewska, Malgorzata; Frisina, N

doi:10.1007/s001980170079

Cited by 77 publications

(70 citation statements)

References 32 publications

(30 reference statements)

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“…This suggests that an important determinant of the often suboptimal bone response to testosterone replacement reported previously may be inadequate prior testosterone treatment, largely due to the pharmacological limitations and inconvenience of the available testosterone products. Our findings on the bone density benefits of sustained, adequate treatment are consistent with findings that AD thalassaemic adolescents taking regular testosterone treatment had higher BMD than others whose testosterone treatment was irregular (42,43). In most previous longer (.…”

Section: Discussionsupporting

confidence: 89%

Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men

Aminorroaya

Kelleher²,

Conway³

et al. 2005

eur j endocrinol

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Objective: Androgen deficiency (AD) leads to bone loss and contributes to osteoporotic fractures in men. Although low bone mineral density (BMD) in AD men is improved by testosterone replacement, the responses vary between individuals but the determinants of this variability are not well defined. Design and methods: Retrospective review of dual energy X-ray absorptiometry (DEXA) of the lumbar spine and proximal femur in men with established AD requiring regular androgen replacement therapy (ART). After a DEXA scan all men were treated with testosterone implants (800 mg, , 6 month intervals). Patients were classified as having a congenital, childhood, or post-pubertal onset, as well as according to the adequacy of treatment prior to their first DEXA scan as untreated, partially treated or well treated. Results: Men with AD requiring regular ART (n ¼ 169, aged 46.3^1.1 years, range 22 -84 years) underwent a DEXA scan prior to being treated with testosterone implants (800 mg, ,6 month intervals). In cross-sectional analysis at the time of the first DEXA scan untreated men (n ¼ 24) had significantly reduced age-adjusted BMD at all four sites (L1 -L4, femoral neck, Ward's triangle and trochanter). Well-treated men (n ¼ 77) had significantly better age-adjusted BMD at all four sites compared with those who were partially treated (n ¼ 66) or untreated (n ¼ 24) with their ageadjusted BMD being normalized. In a longitudinal assessment of men (n ¼ 60) who had two or more serial DEXA scans, at the second DEXA scan after a median of 3 years, men who were previously partially treated (n ¼ 19) or untreated (n ¼ 11) had proportionately greater improvements in BMD, significantly for Ward's triangle (P ¼ 0.025) and the trochanter (P ¼ 0.044) compared with men (n ¼ 30) previously well treated. Conclusions: The present study demonstrates a positive relationship between adequacy of testosterone replacement and BMD in men with overt organic AD. Additionally, the BMD of well-treated AD men approximates that of age-matched non-AD controls. The greatest BMD gains are made by those who have been either untreated or partially treated, and optimal treatment over time (median 3 years) normalizes BMD to the level expected for healthy men of the same age.European Journal of Endocrinology 152 881-886

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Section: Discussionsupporting

confidence: 89%

Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men

Aminorroaya

Kelleher²,

Conway³

et al. 2005

eur j endocrinol

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“…Furthermore, iron chelation has correlated with growth failure and bone abnormalities, and high desferrioxamine dosage has been associated with cartilage alterations (5,6). More puzzling, however, is the observation that, despite the normalization of haemoglobin levels, adequate hormone replacement, and effective iron chelation, patients continue to show an unbalanced bone turnover with an increased resorptive phase resulting in seriously diminished bone mineral density (BMD) (7,8).…”

Section: Thalassaemia and Bone Diseasementioning

confidence: 99%

Bone Disease in Haemoglobin Disorders

Voskaridou

Terpos

2013

Thalassemia Reports

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Bone disease represents a prominent cause of morbidity in patients with thalassaemia and other haemoglobin disorders. The delay in sexual maturation, the presence of diabetes and hypothyroidism, the parathyroid gland dysfunction, the haemolytic anaemia, the progressive marrow expansion, the iron toxicity on osteoblasts, the iron chelators, and the deficiency of growth hormone or insulin growth factors have been identified as major causes of osteoporosis in thalassaemia. Adequate hormonal replacement, effective iron chelation, improvement of hemoglobin levels, calcium and vitamin D administration, physical activity, and smoking cessation are the main to-date measures for the management of the disease. During the last decade, novel pathogenetic data suggest that the reduced osteoblastic activity, which is believed to be the basic mechanism of bone loss in thalassemia, is accompanied by a comparable or even greater increase in bone resorption. Therefore, potent inhibitors of osteoclast activation, such as the aminobisphosphonates, arise as key drugs for the management of osteoporosis in thalassaemia patients and other haemoglobin disorders.

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“…In the absence of vertebral compression (crush) fractures, the diagnosis of osteoporosis is indicated by the presence of both a clinically significant fracture history and BMD Z-score less than or equal to -2.0 SD (22). In some studies (23,24), in order to reduce the u n c o r r e c t e d p r o o f influence of bone size on BMD measurements in the growing skeleton, the apparent volumetric density of the lumbar spine has been calculated using a specific formula (25). In TM patients, it is very common to find low BMD values (osteopenia or osteoporosis) and in some studies up to 90%, even in optimally transfused and chelated patients, as is shown in Table 1 (7,(26)(27)(28)(29)(30)(31).…”

Section: Bone Metabolism In Tm Patientsmentioning

confidence: 99%

“…Vertebral fractures are usually underestimated, and their prevalence varies from 2.6% to 13% (27,36). TM patients, in spite of following a regular transfusional regimen, and receiving adequate sex hormone replacement and chelating therapy, show imbalanced bone turnover with an increased resorptive phase that is not followed by an appropriate neoformation rate, resulting in a decreased BMD, particularly at the vertebral level, where trabecular bone is mostly represented (23,27,(37)(38)(39). In previous studies (14,23), we described a decreased neoformation phase in accordance with Mahachoklertwattana (24) and histomorphometric studies performed by De Vernejoul (40).…”

Section: Bone Metabolism In Tm Patientsmentioning

confidence: 99%

“…The depression of bone formation, even if slight, is surprising because an increase in resorption is generally followed by a corresponding increase in bone formation due to coupling of bone turnover. Numerous acquired factors could lead to the inhibition of osteoblastic activity, such as a defective GH-IGF-I axis, iron deposits in bone, or deferoxamine toxicity (14,23). Many studies (14,23,(37)(38)(41)(42) have shown the increased osteoclast activation in these patients, measuring markers of bone resorption such as urinary levels of N-telopeptide of collagen type I (NTX), serum levels of tartrate resistant acid phosphatase isoform 5b (TRACP-5b), and urinary pyridinium cross-links.…”

Section: Bone Metabolism In Tm Patientsmentioning

confidence: 99%

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Pathogenesis of Thalassemia Major–Associated Osteoporosis: Review of the Literature and Our Experience

Gaudio¹,

Morabito²,

Catalano³

et al. 2018

Jcrpe

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Due to increasing life expectancy in thalassemia major (TM), osteoporosis is emerging as a significant problem. Its aetiology is multifactorial, culminating in increased bone resorption and remodelling. Hypogonadism and marrow expansion seem to play an important role, but iron overload, deferoxamine toxicity, a defective GH-IGF-1 axis and multiple endocrinopathies may represent additional causes of bone damage. Many of these patients, though under appropriate treatment programs, do not achieve normal peak bone mass. The RANK/RANKL/OPG and the Wnt/βCatenin systems work as major mediators of imbalanced bone turnover and bone loss. Additional genetic factors, such as collagen type I alpha 1 and vitamin D receptor gene polymorphisms, may exert some influence on the enhanced fracture risk observed in TM. To date, in spite of adequate hormone replacement, chelating therapy, and acceptable haemoglobin levels, subjects with TM display impaired bone density and imbalanced bone turnover, so the puzzle of the pathogenesis of thalassemia major-induced osteoporosis remains far from being solved.

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Effects of Hormonal Replacement Therapy on Bone Metabolism in Young Adults with Beta-thalassemia Major

Cited by 77 publications

References 32 publications

Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men

Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men

Bone Disease in Haemoglobin Disorders

Pathogenesis of Thalassemia Major–Associated Osteoporosis: Review of the Literature and Our Experience

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