Investigation of bone mineral density and the changes by enzyme replacement therapy in patients with Fabry disease

Nose, Yuma; Fujii, Hideki; Goto, Shunsuke; Kono, Keiji; Okamoto, Hiroaki; Watanabe, Kentaro; Nishi, Shinichi

doi:10.1016/j.ymgme.2023.107634

Cited by 4 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The introduction of Fabry-specific therapies, including enzyme replacement therapies with agalsidase alpha and agalsidase beta, and, more recently, the chaperone migalastat, have substantially improved the prognosis of Fabry disease over the last two decades [15,16]. However, there are limited previous data describing the effects of Fabry-specific therapies on bone outcomes [11].…”

Section: Discussionmentioning

confidence: 99%

“…In comparison, limited comparable analysis exists in FD, where a bone phenotype is less pronounced. Recently, Nose et al found that the commencement of ERT was associated with increases in BMD over two years among males with FD [11]. However, this was a small cohort study and longitudinal BMD data were only available for ten individuals with FD.…”

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

The Effect of Fabry Disease Therapy on Bone Mineral Density

Aitken,

Tiong,

Talbot

et al. 2024

Diseases

View full text Add to dashboard Cite

Fabry disease (FD) is an X-linked lysosomal storage disorder, characterised by the cellular accumulation of globotriaosylceramide due to impaired alpha-galactosidase A enzyme activity. FD may manifest with multisystem pathology, including reduced bone mineral density (BMD). Registry data suggest that the introduction of Fabry-specific therapies (enzyme replacement therapy or chaperone therapy) has led to significant improvements in overall patient outcomes; however, there are limited data on the impact on bone density. The aim of this study was to describe the effect of Fabry-specific therapies on longitudinal changes in bone mineral density (BMD) in FD. We performed a retrospective observational study analysing bone densitometry (DXA) in patients with genetically confirmed FD. Patients were grouped based on the use of Fabry-specific therapies. The between-group longitudinal change in BMD Z-score was analysed using linear mixed effects models. A total of 88 FD patients were analysed (50 untreated; 38 treated). The mean age at first DXA was 38.5 years in the untreated group (84% female) and 43.7 years in the treated group (34% female). There was no significant longitudinal between-group difference in the BMD Z-score at the lumbar spine. However, the Z-score per year at the total hip (β = −0.105, p < 0.001) and femoral neck (β = −0.081, p = 0.001) was significantly lower over time in the treated than the untreated group. This may reflect those receiving therapy having a more severe underlying disease. Nevertheless, this suggests that Fabry-specific therapies do not reverse all disease mechanisms and that the additional management of BMD may be required in this patient population.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

The Effect of Fabry Disease Therapy on Bone Mineral Density

Aitken,

Tiong,

Talbot

et al. 2024

Diseases

View full text Add to dashboard Cite

show abstract

“…In this putative scenario, the activation of IL-6 soluble receptors, able to spread inflammatory signals all over the body, might in part explain some of the clinical presentations of FD, which feature multisystemic damage, also involving tissues not directly affected by Gb3 accumulation, as, for instance, the gastrointestinal system [ 23 , 24 ] or the bone [ 25 , 26 ]. Our data provide further evidence that other biological processes, besides the cellular alterations associated with Gb3 deposition, might participate in the irreversible tissue and organ damage featured in FD, similar to what was found, for instance, in the development of kidney fibrosis in FD [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Soluble Interleukin 6 Receptors in Fabry Disease

Lenzini,

Iori,

Vettore

et al. 2023

JCM

View full text Add to dashboard Cite

Fabry disease (FD) is an X-linked lysosome storage disease that results in the accumulation of globotriaosylceramide (Gb3) throughout the body leading to irreversible target organ damage. As the role of secondary mediators (inflammatory molecules) and their mechanisms has not been fully elucidated, we focused on the interleukin (IL)-6 system in adult FD patients and in matched healthy subjects. To obtain insights into the complex regulation of IL-6 actions, we used a novel approach that integrates information from plasma and exosomes of FD patients (n = 20) and of healthy controls (n = 15). Soluble IL-6 receptor (sIL-6R) levels were measured in plasma with the ELISA method, and membrane-bound IL-6R was quantified in plasma and urinary exosomes using flow cytometry. In FD patients, the levels of soluble IL-6R in plasma were higher than in control subjects (28.0 ± 5.4 ng/mL vs. 18.9 ± 5.4 ng/mL, p < 0.0001); they were also higher in FD subjects with the classical form as compared to those with the late-onset form of the disease (36.0 ± 11.4 ng/mL vs. 26.1 ± 4.5 ng/mL, p < 0.0001). The percentage of urinary exosomes positive for IL-6R was slightly lower in FD (97 ± 1 vs. 100 ± 0% of events positive for IL-6R, p < 0.05); plasma IL-6 levels were not increased. These results suggest a potential role of IL-6 in triggering the inflammatory response in FD. As in FD patients only the levels of sIL-6Rs are consistently higher than in healthy controls, the IL-6 pathogenic signal seems to prevail over the homeostatic one, suggesting a potential mechanism causing multi-systemic damage in FD.

show abstract

“…A T-score of -2.5 or less indicates osteoporosis [7]. A T-score is a calculated value of BMD in the patient when compared to a healthy 20-29-year-old white, female, reference population [13].…”

Section: Methodsmentioning

confidence: 99%

“…Possible causes of osteoporosis and osteopenia include reduced calcium absorption, low vitamin D levels, renal failure, secondary hyperparathyroidism, steroid therapy, and the use of antiepileptic agents for pain control. However, none of which have been clearly linked to FD as being the primary explanation [3][4][5][6][7]. Currently, there are no speci c guidelines for routine bone density assessment and treatment of osteoporosis and osteopenia as part of FD standard of care.…”

Section: Introductionmentioning

confidence: 99%

Assessing Osteopenia and Osteoporosis with Dual-energy X-ray Absorptiometry Studies in Fabry Disease

Shmara,

Lee,

Mgdsyan

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Fabry disease is a rare multi-systemic lysosomal storage disease that affects the heart and kidneys most significantly. An underappreciated manifestation of FD is reduced bone mineral density. Currently, there are no specific guidelines for routine bone density assessments, and treatment of osteoporosis and osteopenia in Fabry disease. Materials and methods To ascertain the frequency of low bone mineral density in FD we studied dual-energy x-ray absorptiometry (DXA) scans obtained as part of routine care from a cohort of 25 individuals followed at the University of California - Irvine Medical Center. The most recent DXA scan results were analyzed from 12 males and 13 females to examine the prevalence of low bone mineral density. In our cohort the mean age was 51 years (median 56 years, range 18-77 years). The Z-scores for all participants and T-scores from postmenopausal women and men ≥ 50-year-old were analyzed and correlated with various measures including disease duration, BMI, renal function (measured by eGFR), plasma GL3, Lyso-GL3, calcium, vitamin D, and alkaline phosphatase levels. Results The average Z-score for all the participants was -1.2±1.3 (range -4.6 to 1.6). Twenty-four percent of all participants (n=6) had significantly low Z-scores below ≤ -2.0. To identify the frequency of subjects with osteopenia, defined as T-score between -1.0 and -2.5and osteoporosis defined as T-score < -2.5, T-scores were analyzed in postmenopausal women (n=8) and men 50 years and older (n=7). Of these 15 individuals, average T-score was -2.2±1.3 (range -5.4 to – 0.3), and 86.7% (n=13) had abnormal results (osteopenia and osteoporosis), 53.3% (n=8) had osteoporosis and 33.3% (n=5) had osteoporosis. We found a significant difference in Z-scores between male (-1.98 ±1.33) and female patients (-0.45 ±0.82) t (23) = 3.487 (p = < 0.001). We did not find any differences in z-scores between different ethnic backgrounds. There was a strong negative correlation between Z-scores and Lyso-GL3 levels [r (23) = -.72, p=.001] and a moderate positive correlation between Z-scores and body mass index (BMI) [r (23) = .43, p=.033]. No correlation was found between Z-scores and calcium levels. There is a strong negative correlation between T-scores and Lyso-GL3 levels [r (8) = -.86, p=.001] and a strong negative correlation between T-scores and participants’ ages at the time of DXA [r (13) = -.57, p=0.028]. There is a strong positive correlation between T- scores and calcium levels [r (12) = .58, p=0.030]. No significant correlation was observed between T-scores and BMI. There was no correlation between Z or T- scores and disease duration, duration of ERT use, renal function (measured by eGFR), GL3, creatinine, vitamin D, or alkaline phosphatase levels. We did not find a significant difference in Z- or T- scores between the individuals based on their use of vitamin D or concomitant antiepileptic medications. Conclusion The findings of this cohort highlight the high prevalence of low bone mineral density in Fabry disease and correlations of low Z and T- scores with elevated levels of Lyso-GL3, and low calcium levels. We did not find correlations with renal function, and vitamin D levels. We discuss etiology, prevention, and treatment strategies for osteopenia/osteoporosis in Fabry disease.

show abstract

Investigation of bone mineral density and the changes by enzyme replacement therapy in patients with Fabry disease

Cited by 4 publications

References 24 publications

The Effect of Fabry Disease Therapy on Bone Mineral Density

The Effect of Fabry Disease Therapy on Bone Mineral Density

Increased Soluble Interleukin 6 Receptors in Fabry Disease

Assessing Osteopenia and Osteoporosis with Dual-energy X-ray Absorptiometry Studies in Fabry Disease

Contact Info

Product

Resources

About