Rhabdomyolysis and myoglobinuria following bisphosphonate infusion in patients with Duchenne muscular dystrophy

Lemon, Jennifer; Turner, Lucy; Dharmaraj, Poonam; Spinty, Stefan

doi:10.1016/j.nmd.2019.05.002

Cited by 8 publications

(7 citation statements)

References 2 publications

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“…Individual study samples comprised between 1 and 520 cases, and the age of patients ranged between 5 and 23 years (5 studies did not report minimum and maximum ages). 4 , 13 , 17 , 20 , 22 Two (11%) studies reported results from randomized controlled trials, 24 , 25 8 (42%) from retrospective cohort studies, 4 , 11 , 13 , 17 , 18 , 20 , 21 , 23 5 (26%) from case studies/series, 10 , 14 , 15 , 19 , 27 2 (11%) from prospective cohort studies, 16 , 26 1 (5%) from a case-control trial, 22 and 1 (5%) from an uncontrolled before-and-after trial. 12 …”

Section: Resultsmentioning

confidence: 99%

Bisphosphonates in Glucocorticoid-Treated Patients With Duchenne Muscular Dystrophy

Landfeldt,

Phung,

Zaman

et al. 2024

Neurology

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Background and Objectives Bisphosphonates are routinely used to treat osteoporosis in patients with Duchenne muscular dystrophy (DMD), a rare, severely debilitating neuromuscular disease. We sought to synthesize and grade benefits and harms evidence of bisphosphonates in glucocorticoid-treated patients with DMD. Methods In this systematic review (PROSPERO identifier: CRD42020157606), we searched MEDLINE, CINAHL, Embase, PsycINFO, Web of Science, and CENTRAL for articles published from inception up to and including March 31, 2023, reporting results in any language from any study type. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Results We identified 19 publications involving 1,010 children and adults from 12 countries across all inhabited continents except South America. We found high-quality evidence that bisphosphonates significantly increase the areal lumbar spine bone mineral density (BMD) Z score in glucocorticoid-treated patients with DMD. The greatest improvements were recorded in controlled settings among patients treated with intravenous zoledronate. Evidence of benefits to fracture risks was inconclusive and/or of low quality, primarily due to lack of controlled data and small samples. Bisphosphonates were generally well-tolerated, although adverse events related to the first infusion (i.e., “acute phase reaction”) were frequently reported. Discussion There is high-quality evidence supporting the use of bisphosphonates to increase the areal lumbar spine BMD Z score in patients with DMD and glucocorticoid-induced osteoporosis. Our synthesis and grading affirm current recommendations put forward in the 2018 DMD Clinical Care Considerations and should be helpful in raising awareness about anticipated benefits of bisphosphonates, prevailing unmet needs, and potential safety issues in their use.

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Section: Resultsmentioning

confidence: 99%

Bisphosphonates in Glucocorticoid-Treated Patients With Duchenne Muscular Dystrophy

Landfeldt,

Phung,

Zaman

et al. 2024

Neurology

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“…zoledronic acid treatment, in addition to vitamin D and calcium, leads to improvements in bone mass scores compared with vitamin D and calcium alone in Duchenne Muscular Dystrophy patients treated with corticosteroids. It was generally found to be safe and well tolerated apart from marked acute-phase reaction on first exposure in these people with some benefit in reducing pain [ 45 , 46 , 47 ]. Similarly, it is effective in glucocorticoid-induced osteoporosis in chronic pediatric illnesses associated with osteoporotic fractures [ 46 ], but the mechanism of action is not known.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, it is effective in glucocorticoid-induced osteoporosis in chronic pediatric illnesses associated with osteoporotic fractures [ 46 ], but the mechanism of action is not known. In our opinion, it is likely that the reported case reports of rhabdomyolysis and myoglobinuria following the administration of zoledronic acid in Duchenne Muscular Dystrophy can be associated with the interactions with muscle KATP channels [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Zoledronic Acid Blocks Overactive Kir6.1/SUR2-Dependent KATP Channels in Skeletal Muscle and Osteoblasts in a Murine Model of Cantú Syndrome

Scala

Maqoud

McClenaghan

et al. 2023

Cells

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Cantú syndrome (CS) is caused by the gain of function mutations in the ABCC9 and KCNJ8 genes encoding, respectively, for the sulfonylureas receptor type 2 (SUR2) and the inwardly rectifier potassium channel 6.1 (Kir6.1) of the ATP-sensitive potassium (KATP) channels. CS is a multi-organ condition with a cardiovascular phenotype, neuromuscular symptoms, and skeletal malformations. Glibenclamide has been proposed for use in CS, but even in animals, the drug is incompletely effective against severe mutations, including the Kir6.1wt/V65M. Patch-clamp experiments showed that zoledronic acid (ZOL) fully reduced the whole-cell KATP currents in bone calvaria cells from wild type (WT/WT) and heterozygous Kir6.1wt/V65MCS mice, with IC50 for ZOL block < 1 nM in each case. ZOL fully reduced KATP current in excised patches in skeletal muscle fibers in WT/WT and CS mice, with IC50 of 100 nM in each case. Interestingly, KATP currents in the bone of heterozygous SUR2wt/A478V mice were less sensitive to ZOL inhibition, showing an IC50 of ~500 nM and a slope of ~0.3. In homozygous SUR2A478V/A478V cells, ZOL failed to fully inhibit the KATP currents, causing only ~35% inhibition at 100 μM, but was responsive to glibenclamide. ZOL reduced the KATP currents in Kir6.1wt/VMCS mice in both skeletal muscle and bone cells but was not effective in the SUR2[A478V] mice fibers. These data indicate a subunit specificity of ZOL action that is important for appropriate CS therapies.

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“…26 Although intravenous BPs appear to be safe, caution is needed as patients with disuse or GC-induced osteoporosis, including patients with DMD, may be at higher risk for developing acute-phase reactions, electrolyte disturbances, and rhabdomyolysis after intravenous BP infusions. [27][28][29] Oral BPs may have lower bioavailability, but are generally better tolerated and have fewer side effects when compared with intravenous BPs. In addition, oral BPs are more convenient to administer.…”

Section: Discussionmentioning

confidence: 99%

The effect of oral bisphosphonate therapy on vertebral morphometry and fractures in patients with Duchenne muscular dystrophy and glucocorticoid‐induced osteoporosis

et al. 2021

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Introduction/Aims: Glucocorticoid-induced osteoporosis with vertebral fractures is frequent in patients with Duchenne muscular dystrophy (DMD). In this study, we evaluated the effects of oral bisphosphonate (BP) therapy on the prevalence and severity of vertebral fractures by vertebral morphometry assessment. Methods: We reviewed the records and radiographs of patients with DMD who had been treated with oral BP (weekly alendronate) and had undergone routine spine radiographic monitoring for glucocorticoid-induced osteoporosis at Cincinnati Children's Hospital Medical Center between 2010 and 2017. Study outcomes were thoracic and lumbar vertebral fracture prevalence and severity, assessed by Genant semiquantitative grading of vertebral morphometry, for up to 5 years of treatment.Results: Fifty-two patients (median age, 11.8 years; 88% prepubertal; 31% nonambulatory) had been treated with long-term glucocorticoids (median duration, 4.7 years at BP start). Most patients (75%) had mild vertebral height loss or fractures

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Rhabdomyolysis and myoglobinuria following bisphosphonate infusion in patients with Duchenne muscular dystrophy

Cited by 8 publications

References 2 publications

Bisphosphonates in Glucocorticoid-Treated Patients With Duchenne Muscular Dystrophy

Bisphosphonates in Glucocorticoid-Treated Patients With Duchenne Muscular Dystrophy

Zoledronic Acid Blocks Overactive Kir6.1/SUR2-Dependent KATP Channels in Skeletal Muscle and Osteoblasts in a Murine Model of Cantú Syndrome

The effect of oral bisphosphonate therapy on vertebral morphometry and fractures in patients with Duchenne muscular dystrophy and glucocorticoid‐induced osteoporosis

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