ENMC recommendations for optimizing bone strength in neuromuscular disorders


Number 274
Date 19 January 2024

ENMC recommendations for optimizing bone strength in neuromuscular disorders.

274th ENMC international Workshop

Location: Hoofddorp, The Netherlands

Title: ENMC recommendations for optimizing bone strength in neuromuscular disorders.

Date: 19-21 January 2024

Organizers: Leanne Ward (Canada), Antimo Moretti (Italy), David Weber (USA) and Nicol Voermans (The Netherlands)

Translation of this report by:
German: Silke Schlüter
Dutch: Ingrid de Groot
Italian: Chiara Panicucci
French: Leanne Ward
Polish: Anna Kostera - Pruszczyk

Participants: Ingrid de Groot (The Netherlands), Michela Guglieri (UK), Claire Wood (UK), Sara Liguori (Italy), Giovanni Iolascon (Italy), Anna Kostera-Pruszczyk (Poland), Corrie Erasmus (The Netherlands), Marianne de Visser (The Netherlands), Leanne Ward (Canada), David Weber (USA), Chiara Panicucci (Italy), Silke Schlüter (Germany), Nicola Crabtree (UK), Andrea del Fattore (Italy), Kristl Claeys (Belgium), Anne Dittrich (The Netherlands), Madelon Kroneman (The Netherlands), Jarod Wong (UK), Nicol Voermans (The Netherlands), Antimo Moretti (Italy).

The 274rd ENMC workshop titled ‘ENMC recommendations for optimizing bone strength in Neuromuscular Disorders’ was held on January 19-21, 2024 in Hoofddorp, The Netherlands. Twenty participants, including three patient representatives, were brought together to discuss different aspects of bone strength in people with neuromuscular disorders (NMDs). The goals of the workshop were to summarize the literature, identify knowledge gaps and create plans to improve clinical care and guide future research. The group of participants included of experts in the fields of bone health and neuromuscular medicine (along with the patient voice).

In the opening session of the workshop, the patient representatives presented the results of a survey completed by more than 500 people with NMDs. This survey showed that many people with NMDs are suffering from bone fractures and/or osteoporosis. Furthermore, they stated that the prevention and treatment of bone health issues are not part of the usual care provided to people with NMDs. This was felt to be a significant problem and the respondents wished for greater awareness of fractures among both health care providers and people with NMDs and for  more structural approach for the evaluation, prevention and treatment of bone fragility. In parallel, a survey among clinicians via EURO-NMD was performed. The preliminary results showed moderate to good awareness of the importance of bone strength, but lack of medical training on this topic. The current clinical practice appeared to be variable with respect to diagnostics and treatment.

Terminology, definitions, and normal bone strength development  were discussed. In people with NMDs, bone strength can be compromised due to bone-muscle unit impairment related to both biomechanical and biochemical alterations. Reduced biomechanical loading due to the inability to bear weight normally, caused by muscle weakness and immobility, may lead to decreased bone mineral density (BMD) and hinder the achievement of normal peak bone mass. The interplay between muscles and bones is complex, also involving signaling pathways regulated by myokines and osteokines, factors produced by the muscle and bone tissue respectively.

Chronic exposure to steroids and delayed puberty, as is common for people with  Duchenne muscular dystrophy (DMD), for example, further worsen bone strength. Nutritional difficulties can additionally weaken bones. All of these factors contribute to a higher risk of secondary osteoporosis and fragility fractures in NMDs, with a great burden on quality of life (premature loss of ambulation, loss of independency in daily activities, impact on caregivers).

In clinical practice and research, various methods are used to indirectly estimate bone quality and strength. These include measuring BMD by dual-energy X-ray absorptiometry (DXA), bone health index by handX-ray and bone size and shape by peripheral quantitative computed tomography (pQCT) scans. Assessing vertebral fractures in people with DMD or other conditions treated with prolonged high dose steroids is recommended through lateral thoraco-lumbar spine X-rays. However, using these tests can be challenging due to technical issues having to do with the machines, patient conditions (severe scoliosis, contractures, pain during positioning), and limitations in data interpretation because of incomplete reference data, and uncertain  cut-offs to identify people at risk of having a fracture.

There is an urgent need for a fragility fracture risk tool to identify people with NMDs at risk of imminent fractures for the initiation of preventive bone-targeted treatment. Anti-resorptive drugs, primarily bisphosphonates, have the most evidence in NMDs, with limited data on denosumab or anabolic agents. Denosumab has the potentially serious complication of hypercalcemic “rebound”, rendering the use of this agent challenging. Alongside pharmacological therapies, physical activity, including both unstructured and structured exercises (strength and weight-bearing training), have been recommended. However, there is no consensus on when to start and how long to continue bone-protective therapies. As the most widely-used agents in clinical practice to prevent and treat bone fragility irrespective of underlying disease, the safety and efficacy of bisphosphonates has been studied for decades. While the use of bisphosphonates in people with NMD has been adapted from observations in other disease settings, their long-term efficacy and safety data specifically in NMD is lacking.

Most of the bone-related evidence in NMDs has been developed in the pediatric setting, in particular in children with DMD. Information on the monitoring and treatment of  bone health issues in other NMDs is still emerging and is not included in current care recommendations, as acknowledged by patients. In contrast, in the general population, most research and clinical care guidelines have been focuses on the prevention and treatment of post-menopausal osteoporosis. There is a knowledge gap on bone strength in adolescence and early adulthood in patients who do not have normal motor abilities. Educating clinicians and patients on bone issues is crucial to implement bone management in all NMDs.

The last day of the workshop plans were made for further research, and initiatives for disseminating knowledge about this important topic were identified:

  1. Muscle and bone strength are intimately linked, and therefore bone strength and the risk of fractures needs to be an integrated part of the NMD patient’s overall health assessment.
  2. The patient’s clinical context and related disease milestones guide understanding the risk of bone fragility more than a single diagnostic test.
  3. Trivialization of single and peripheral low-trauma fractures is inappropriate in patients with neuromuscular disorders.
  4. Longitudinal skeletal phenotyping is key to understanding the individual’s bone health trajectory and thereby need for progressive intensification of bone health management.
  5. Multi-site skeletal assessments that are tuned to the specific muscle-bone phenotype are necessary to understand the spectrum of an individual patient’s bone health phenotype.
  6. The evaluation of an individual’s potential to recover from their risk of osteoporosis without bone-targeted therapy is pivotal to the management paradigm.
  7. Multi-disciplinary osteoporosis prevention and treatment, including an expert in skeletal health, is the cornerstone of timely and effective bone health management.

A full report of the conference will be published in Neuromuscular Disorders.