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Safety and efficacy of teriparatide treatment for severe osteoporosis in patients with Duchenne muscular dystrophy

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Abstract

Summary

Osteoporosis is a major concern in patients with Duchenne muscular dystrophy. In this novel study of teriparatide treatment in 6 patients with severe osteoporosis, bone health (fractures, vertebral morphometry, and DXA) remained stable, with no adverse events. These findings will help inform future osteoporosis research in this challenging population.

Introduction

Despite standard therapy with vitamin D and bisphosphonates (BP), many patients with Duchenne muscular dystrophy (DMD) continue to sustain fragility fractures due to long-term glucocorticoid treatment and limited mobility. We aimed to evaluate the safety and efficacy of teriparatide for the treatment of severe osteoporosis in adolescent and young adult patients with DMD.

Methods

We prospectively treated 6 patients with DMD who had severe osteoporosis with teriparatide 20 mcg subcutaneously daily for 1–2 years. Inclusion criteria were long-term glucocorticoid therapy, and severe osteoporosis despite treatment with BP, or intolerance to BP. We examined long bone and vertebral fracture outcomes, including vertebral morphometry measures, bone mineral density and content, bone formation markers, safety indices, and adverse events.

Results

The mean age at teriparatide start was 17.9 years (range 13.9–22.1 years). All 6 patients were on daily glucocorticoids (mean ± SD; duration 10.9 ± 2.5 years) and 5 were non-ambulatory. Five patients had been treated with BP for 7.9 ± 4.2 years. All had vertebral and a history of long bone fragility fractures at baseline. Vertebral heights and Genant fracture grading remained stable. Long bone fracture rate appeared to decrease (from 0.84/year to 0.09/year); one patient sustained a long bone fracture at 6 months of treatment. Trajectories for change in bone mineral density and content were not different post- vs. pre-teriparatide. Procollagen type 1 amino-terminal propeptide (P1NP) increased, while laboratory safety indices remained stable and non-concerning. No adverse events were observed.

Conclusion

In six patients with DMD treated with teriparatide for severe osteoporosis, we observed stable bone health and modest increases in P1NP, without safety concerns. Further studies are needed to better understand teriparatide efficacy for treatment of osteoporosis in patients with DMD.

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Abbreviations

aBMD:

Areal bone mineral density

BMAD:

Bone mineral apparent density

BMD:

Bone mineral density

BMC:

Bone mineral content

BP:

Bisphosphonate(s)

DMD:

Duchenne muscular dystrophy

DXA:

Dual X-ray absorptiometry

eGFR:

Estimated glomerular filtration rate

GC:

Glucocorticoid(s)

GIO:

Glucocorticoid-induced osteoporosis

LDF:

Lateral distal femur

LS:

Lumbar spine

P1NP:

Procollagen type 1 amino-terminal propeptide

PTH:

Parathyroid hormone

rhPTH:

Recombinant human PTH

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Author notes

  1. N. Nasomyont and C. Keefe contributed equally to this work and both should be considered first author.

Authors and Affiliations

  1. Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 7012, Cincinnati, OH, 45229-3026, USA

    N. Nasomyont, J. Khoury & M. M. Rutter

  2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    N. Nasomyont, C. Tian, J. Khoury, E. Jackson & M. M. Rutter

  3. Diabetes and Endocrinology, Helen DeVos Children’s Hospital, Grand Rapids, MI, USA

    C. Keefe

  4. Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    C. Tian & I. Rybalsky

  5. Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    L. Hornung & J. Khoury

  6. Yale University, New Haven, CT, USA

    J. C. Tilden

  7. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    P. Hochwalt

  8. Division of Nephrology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    E. Jackson

  9. Department of Pediatrics, University of Massachusetts Memorial Children’s Medical Center, University of Massachusetts Medical School, Worcester, MA, USA

    B. L. Wong

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Nasomyont, N., Keefe, C., Tian, C. et al. Safety and efficacy of teriparatide treatment for severe osteoporosis in patients with Duchenne muscular dystrophy. Osteoporos Int 31, 2449–2459 (2020). https://doi.org/10.1007/s00198-020-05549-z

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