## 8 Specific Groups  
While the principles with respect to at-risk children mapped out previously in this article apply to all high-risk groups, the following describes additional disease-specific nuances in the management of patients who fall into three groups: those with profound intellectual and multiple disabilities, those with neuromuscular conditions otherwise, and children receiving a therapeutic ketogenic diet for the treatment of intractable seizures. Children with profound intellectual and multiple disabilities (PIMD) form an extremely heterogeneous group regarding cause, level of functioning, and co-morbidities [74]. A GMFCS of four or five in combination with a severe intellectual disability (IQ < 30 or developmental age < 2 years), regardless of the underlying disease, is often used as a criterion for PIMD. Low BMD and secondary osteoporosis are highly prevalent co-morbidities in PIMD. As low BMD often goes unnoticed, a (low-impact) fracture is a common presenting sign of low BMD or osteoporosis. Since children with PIMD are frequently limited in their communication skills, there can be a significant delay in noticing these complications. [PERSON] et al. reported a delay in diagnosis of a fracture in half of the patients with cerebral palsy with an average delay of 10 days [75], stressing the need for a high index of suspicion in this population. Incidence rates for fractures in children with PIMD are scarce. However, ample literature regarding fractures and low BMD in children and adults with cerebral palsy is available. As the level of (motor) functioning in severe cerebral palsy (GMFCS 4 or higher) and co-morbidities (e.g., epilepsy) in cerebral palsy in PIMD are fairly similar, these groups can be considered interchangeably regarding osteoporosis and low BMD. The incidence rates for fractures in children with severe cerebral palsy have been reported to be around 4% [76]. However, these numbers vary greatly. A systematic review by [PERSON], including 21 studies in children with severe cerebral palsy, reported incidence rates of fractures varying from 2.7-23% [27]. The prevalence of low BMD was higher, with reported rates of 27-77%. Several studies have evaluated low BMD and secondary osteoporosis risk factors in children with cerebral palsy/PIMD. Although the reported significance of the risk factors varies, non-ambulatory status, feeding difficulties, and anticonvulsant use are repeatedly outlined as the foremost. Several studies have also shown tube feeding as an independent risk factor for low BMD [76; 77], although it is unclear if this is a consequence of more excessive feeding difficulties. Other risk factors that have been reported are dietary deficits (calcium, vitamin D) and the use of other drugs, such as proton pump inhibitors [78], solely progestin-containing contraceptives [79], and delayed puberty. Of course, sustaining previous fractures has also been shown to be an important risk factor [80], as is low BMD. Conversely, laboratory studies (e.g., calcium, phosphorus, alkaline phosphatase) have not been shown to correlate with low BMD. As calcium and phosphatase levels in the blood are maintained at a constant level at the expense of bone composition, this is not unimaginable, but unremarkable blood tests can give the clinician a false sense of security. Diagnosing and following up on low BMD in children with PIMD deserves special attention. Measurement by DXA, including DXA-based vertebral fracture assessment (or baseline spine radiograph), is considered the gold standard, but its availability in hospitals is limited. Furthermore, movement during measurement, scoliosis, or contractures can negatively influence the measurements. Alternatives, such as the aforementioned digital X-ray radiogrammetry, have been proven to correlate well with DXA [81] in healthy children. This technique has also been investigated in children with PIMD and seems feasible, with the exception of children with (severe) anatomical deformities [20].