1.1 It “makes sense” to “armour” against fractures

Young people, parents and health professionals all discussed how preventative IV bisphosphonates should be used if they could delay or prevent fractures: “I’d say it’s a good idea to do it before you have [a fracture], so then it can help prevent it from ever happening” (YP17, aged 17, # aged 12).

Preventative treatment was discussed as of value as it “could give another bit of armour, bit [of] protection” (P5, C aged 7) to their child/young person and prevent or delay the subsequent consequences of experiencing fractures, particularly pain and limited mobility: “I really wish we had [the preventative infusions]... I think he would still be walking quite well now if we had of done that... he wasn’t exercising as much because of the back pain” (P12, C aged 14, #aged 12).

Parents questioned current clinical approaches for monitoring and managing bone health and fractures, which required a child/young person to experience a fracture before action was taken (i.e., bisphosphonate therapy was provided): “how so incredulous that we would wait until he broke his, something, to then begin the treatment that would prevent him doing that... that’s mad surely there’s something we can do to prevent it” (P8, C aged 10).

Both parents and health professionals discussed how preventative treatment would “prevent stuff rather than firefighting” (P9, C aged 12, # aged 10). A more proactive approach to initiation of treatment when there are signs of deterioration of bone health could help prevent the vertebral fracture cascade: “I’m perhaps a little bit more proactive for example with children on daily dose or who are for example on deflazacort... if the bone density starts to go down, if there are some changes in the bone in your knowledge of this type of steroid that they are having... and the regime, maybe my approach is a little bit more proactive” (HP5, neuromuscular clinician).

Parents and health professionals advised that preventative bisphosphonate therapy “makes sense... because a lot of these will end up on bisphosphonate” (HP10, consultant endocrinologist/bone metabolism). Parents compared preventative bisphosphonate therapy with other preventative medications that children/young people took for their health, such as the use of treatment to prevent DMD related cardiac dysfunction: “for argument’s sake, for cardiology, we, I argued for prophylactic medication... he hasn’t got any issues with his heart at this point. So, I tend to think it did make a difference” (P17, C aged 17, # aged 12).

1.2 Focusing on the “end goal”

Parents and young people discussed how the burden and impact of the administration of preventative bisphosphonate therapy and “feeling a bit rotten for a few hours” (P14, C aged 11, #) could be balanced against the potential benefits of treatment: “there is an end goal that we are trying to reach, or you know, a step that we are taking” (P6, C aged 7).

Young people identified that the burden and impact of bisphosphonate therapy was short-lived compared to the impact fractures had on their life: “it’d be worth it in the long run [having preventative IV bisphosphonate treatment] ‘cos then if you think about it, just a day every four months [for treatment] instead of it being four weeks out of everything and not being involved in school and stuff [for fractures]... I’d say it would be an improvement to that” (YP7, aged 16, # aged 14).

Health professionals and parents discussed how the short-term burden of treatment could be reduced by having “the first ones [infusions] are done in the central areas and the rest could be done more locally” (HP5, neuromuscular clinician) or by having infusions “coordinated… for like a whole day” (P18, C aged 11, # aged 9) alongside other appointments.

The burden of hospital visits was “no bother” (P19, C aged 15) to some parents who considered “travel and time... low down on the list” (P9, C aged 12, # aged 10) compared to the benefits of the end goal in protecting their child’s/young person’s bone health. Parents had accepted that monitoring and managing their child’s/young person’s DMD and health required regular hospital visits or taking time off school: “the burden of hospital appointments… it becomes part of your normal really. So we’re used to... driving an hour and a half to go to a 15-minute appointment… [it] becomes a normal way of life” (P2, C aged 10, # aged 8).

2.1 “Strong enough case”, endorsement depends on the evidence and advice

Parents explained that any decisions they were involved in about preventative bisphosphonate therapy would depend on their access to and understanding of information about treatment. Specifically, decisions would depend on if the evidence presented a “strong enough case” as to “why it’s recommended” (P4, C aged 15) and whether health professionals could “answer all the questions that we have, then we are in a position to make a decision” (P6, C aged 7).

Parents discussed that they would be more likely to support preventative IV bisphosphonate use if health professionals or other families of young people with DMD recommended it: “if this is what your professional clinicians are suggesting that you do and also if other people in the community are doing it as well. I think people would be happy to kind of go along with that” (P2, C aged 10, # aged 8).

An important part for parents of participating in treatment decisions was that information was clearly explained and communicated to them in “plain English” (P1): “if an endocrinologist says we want to start this infusion, where this weird name, which is an acid and we’re like what does that mean? What does it do? Why are we doing that? How does that fit in with everything else... this is what the advantages are. This is the disadvantages. This is what you know your first infusion there may be a reaction, but after that it tends to calm down” (P1, C aged 13, # aged 8).

Health professionals discussed that without a strong evidence base, they were “a bit hesitant to start doing it because you’re giving something that they may not need for unclear benefit.” (HP10, consultant endocrinologists/bone metabolism). This led health professionals to highlight the need for future research exploring the use and effectiveness of preventative IV bisphosphonate therapy: “sounds like an excellent idea [getting data on preventative bisphosphonate therapy]... whether it’s done as research or changing standard of care, some sort of ongoing monitoring or... registry or something prospective to monitor outcomes... would be important” (HP5, neuromuscular clinician).

The benefit of preventative treatment needed to be strong, as health professionals raised the resource implications of implementation: “we have more than 100 patients, how feasible is that? I treat more than 100 patients every six months with an IV bisphosphonate? Even if you tell me that is what needs to be done, actually it will take years to implement [in the] NHS to be able to support this” (HP23, neuromuscular clinician).

Whilst much of the discussion focused on the administration of intravenous preventative treatment with bisphosphonates, both parents and health professionals discussed how if oral bisphosphonates “was felt to be beneficial to them, I expect they [families] probably would be quite accepting of that” (HP8, consultant endocrinologists/bone metabolism). Families would be likely to have “a reasonable amount of interest” (HP21, consultant endocrinologist) in oral bisphosphonates compared to intravenous bisphosphonates given as preventative treatment in DMD.

However, health professionals expressed concerns that “there are problems potentially if [oral bisphosphonates are] not taken... quite strictly” (HP8, consultant endocrinologists/bone metabolism) and required careful monitoring due to risks to the patient: “I was always told you’ve got to be very, very careful if it’s not taken as prescribed, it can cause quite a few problems... it would worry me of the prophylactic use of the oral bisphosphonates… I’m not saying it hasn’t got a place, but... it would need to be very carefully monitored” (HP9, endocrine bone nurse specialist).

The use of oral bisphosphonate therapy in improving bone outcomes (bone density and fracture) in DMD was also lacking in evidence: “I don’t believe there’s very good evidence that oral bisphosphonates are as effective as IV in children... it would essentially require some research to know whether actually oral bisphosphonates do reasonably improve your bone density and prevent fracture” (HP25, consultant endocrinologist/bone metabolism).

2.2 Endorsement “depends on people’s circumstances”

Young people and parents discussed that families should be given a choice about preventative bisphosphonate treatment: “I think you should offer people, like whether they’re walking or not, the infusion and if they don’t think they need it or want it, then that’s their choice in the end” (YP4, aged 15). Parents described that these discussions and decisions should involve children/young people with DMD, and the outcome would depend on each individual. For some children/young people, parents explained “if you explained it to him... he’d be quite happy [to have the therapy]” (P14, C aged 11, #) whilst for others who struggled with invasive procedures, “to even get him in there, I think would entail quite a lot of bribery and things” (P8, C aged 10).

Some young people, parents and health professionals reported that a preventative approach might be less beneficial or not necessary for children/young people who were non-ambulatory or on certain corticosteroid regimens: “for people that aren’t walking, I don’t really see the point... unless I was gonna be stupid and dangle my legs in front of my wheels. I’ve got no way of really breaking my bones unless I tip my chair up somehow” (YP4, aged 15).

Parents discussed that attending for intravenous preventative bisphosphonate therapy may be dependent on individual family circumstances, such as work flexibility: “it also depends on people’s circumstances... [my partner] works from home and I’m self-employed so we can get to the hospital for these things. I know if you’ve got two parents that are working, it is finding that time” (P3, C aged 9, # aged 7). Health professionals’ opinions about the importance of individual circumstances in making decisions about preventative treatment were linked to a young person’s clinical presentation, such as targeting treatment to a “higher risk group” (HP25, consultant endocrinologists/bone metabolism) linked to a specified “threshold” (HP24, consultant endocrinologist): “some have all these other issues that we’ve talked about, you know, the monitoring, needle phobia, just depressed and withdrawn and isolated and all those other things” (HP1, paediatrician with interest in endocrinology).

3.1 They “go through enough as it is”, the burden on children, young people and parents

Parents discussed how children/young people “go through enough as it is” (P4, C aged 15) without having additional preventative bisphosphonate therapies. It was important to parents that children/young people “have fun, they don’t need to spend you know so much time in hospital” (P18, C aged 11,# aged 9).

The short-term “nasty” (HP1, paediatrician with interest in endocrinology) and “horrible side effects” (P15) and potential long-term effects on the child’s/young person’s health was a concern for some parents and health professionals: “I worry about the long-term issues if we’re going to start bisphosphonates even earlier. What’s that going to do sort of further down the line, are we going to cause another set of problems?” (HP20, neuromuscular clinician).

Travelling to and attending hospital for preventative bisphosphonate therapy was described mostly by health professionals as being “quite onerous” (HP21, consultant endocrinologist) for families. Some young people and parents identified the time travelling to and attending frequent appointments as a “bit of a hassle” (YP4, aged 15).

Young people and health professionals identified needle phobia as a factor which may influence treatment decisions, this “might put someone off [preventative bisphosphonate therapy]... having a needle injected and cannulation” (YP17, aged 17, # aged 12).

Starting and managing new treatments could be anxiety-provoking for some parents: “it’s a lot to take on when you start one form of medication, so the... thought of doing it at the same time as the steroids at the start, I think would have been a lot for us to worry about” (P3, C aged 9, # aged 7).

The burden associated with preventative bisphosphonate therapy meant that some parents and health professionals were hesitant to have or recommend preventative therapy: “if you can avoid it, avoid it and if everything else looks fine then avoid it” (P15, C aged 14, # aged 11).

3.2 “Beyond bisphosphonate”, fracture prevention is a “whole package of advice”

Health professionals and some parents believed “there’s other things... that could be encouraged” (P17, C aged 17 # aged 12) “beyond bisphosphonate” (HP3, consultant endocrinologist) for bone health protection and fracture prevention. They identified alternative non-invasive approaches which should be provided as a “whole package of advice” (HP2, specialist physiotherapist). Examples include monitoring and managing “weight gain” (HP3, consultant endocrinologist), “having a specialist diet where it’s more high in vitamin D and like omegas... calcium... supplements” (P18, C aged 11, # aged 9) and preserving mobility and muscle function: “the biggest prevention would be movement… movement for as long as possible” (HP26, consultant endocrinologist/bone metabolism).

Health professionals felt it was important for children/young people and parents to be aware of and understand fracture risks (for example, risky behaviours, safe transfers) to reduce the likelihood of fractures: “weighing up some of the risks and not sort of taking part in risky behaviours... making sure they’re wearing their seat belts, not taking undue risks when transferring at that late ambulation stage... if we can actually prevent [fractures] from happening just through practical ways, that would be much better” (HP2, specialist physiotherapist).

However, health professionals noted that there was also a lack of evidence or guidance on the effectiveness of these alternative preventative approaches: “some families ask me whether taking calcium and vitamin D does help... the hard thing is again we don’t know... I can’t turn around and say I promise that if you keep the vitamin D above 75 your bones are going to definitely be better” (HP26, consultant endocrinologist/bone metabolism).

New and innovative methods to monitor and manage bone health in DMD have been developed, such as vamorolone and “better-quality imaging” (HP26, consultant endocrinologists/bone metabolism), that may identify very early signs of bone fragility. Health professionals also questioned whether bisphosphonate treatments would be the best approach to bone protection and fracture prevention in the future: “the newer bone sparing steroids such as vamorolone, using that more or going to develop more that kind of better anti-inflammatory for treatment would be one pathway that we need to lead... making sure that the muscle health is maintained better” (HP27, neuromuscular clinician).