A practical guide to the diagnosis and management of osteoporosis in childhood and adolescence

Abstract

Osteoporosis in childhood distinguishes itself from adulthood in four important ways: 1) challenges in distinguishing otherwise healthy children who have experienced fractures due to non-accidental injury or misfortunate during sports and play from those with an underlying bone fragility condition; 2) a preponderance of monogenic "early onset" osteoporotic conditions that unveil themselves during the pediatric years; 3) the unique potential, in those with residual growth and transient bone health threats, to reclaim bone density, structure, and strength without bone-targeted therapy; and 4) the need to benchmark bone health metrics to constantly evolving "normal targets", given the changes in bone size, shape, and metabolism that take place from birth through late adolescence. On this background, the pediatric osteoporosis field has evolved considerably over the last few decades, giving rise to a deeper understanding of the discrete genes implicated in childhood-onset osteoporosis, the natural history of bone fragility in the chronic illness setting and associated risk factors, effective diagnostic and monitoring pathways in different disease contexts, the importance of timely identification of candidates for osteoporosis treatment, and the benefits of early (during growth) rather than late (post-epiphyseal fusion) treatment. While there has been considerable progress, a number of unmet needs remain, the most urgent of which is to move beyond the monotherapeutic anti-resorptive landscape to the study and application of anabolic agents that are anticipated to not only improve bone mineral density but also increase long bone cross-sectional diameter (periosteal circumference). The purpose of this review is to provide a practical guide to the diagnosis and management of osteoporosis in children presenting to the clinic with fragility fractures, one that serves as a step-by-step "how to" reference for clinicians in their routine clinical journey. The article also provides a sightline to the future, emphasizing the clinical scenarios with the most urgent need for an expanded toolbox of effective osteoporosis agents in childhood.

Keywords: bisphosphonate; bone mineral density; children; chronic illness osteoporosis; fractures; osteogenesis imperfecta; osteoporosis; pamidronate.

Figure 1

The first step in evaluating a child with bone fragility is to rule out rickets, consider that the child may have been subjected to non-accidental injury, and understand whether the child presents in a clinical context known to be associated with bone fragility or not (the latter, referred to as “undifferentiated bone fragility”).

Figure 2

The second step in evaluating a child with bone fragility is to comprehensively assess the child’s skeletal phenotype and, in so doing, search for signs of primary versus secondary osteoporosis.

Figure 3

It is now known that numerous underlying conditions can cause or exacerbate a predisposition to bone fragility in the chronic illness setting. The most frequent diseases and their treatments which predispose to secondary osteoporosis in children, are listed here.

Figure 4

This figure describes the magnitude of supporting evidence that is needed to trigger a bone health evaluation in relationship to fracture characteristics, a key component of the bone fragility assessment. For example, a single low-trauma femur, humerus, or vertebral fracture at presentation means that “ less clinical supporting evidence” is needed to trigger the bone health evaluation, given the seriousness of such fractures. On the other hand, more trivial fractures such as fingers and toes may necessitate “more supporting clinical evidence” to trigger the bone health evaluation (depending on whether there is a clinical context known to be associated with bone fragility, in which case even more trivial fractures may be significant). A comprehensive history, physical examination, and review of the x-ray fracture features provide the necessary information to help guide the decision to proceed with a formal bone health evaluation.

Figure 5

These figures (A, B) provide a framework for classifying primary osteoporosis presenting in childhood.

Figure 6

A proposed approach to the diagnosis of osteoporosis in children. After a careful diagnostic pathway, children will typically fall into one of three categories: a. primary osteoporosis due to a confirmed monogenic etiology, b. secondary osteoporosis due to an underlying medical condition or its treatment which predisposes to an increased risk of fractures, or c. “fractures in otherwise healthy children” (middle bottom). In cases of primary and secondary osteoporosis, even a single, low-trauma fracture may be sufficient to diagnose the child with osteoporosis, even if BMD Z-scores are normal. In the absence of a discrete etiology uncovered by the diagnostic process (middle bottom), a more conservative definition of osteoporosis is proposed in order to prevent children who were unfortunate during sports or play from being over-diagnosed with osteoporosis.

Figure 7

Once the child has been diagnosed with osteoporosis, the next step is to determine whether the child has the potential for “spontaneous, medication-unassisted recovery.” This is important because the pediatric skeleton has tremendous potential to recover from osteoporosis in those with waning risk factors plus residual growth potential.

Figure 8

This figure provides an approach to gauge whether a child has the capacity to undergo spontaneous (medication-unassisted) recovery from osteoporosis, obviating the need for osteoporosis drug therapy.

Figure 9

If a child has limited potential for spontaneous recovery from osteoporosis, the next step is to treat with the current standard of care, intravenous bisphosphonate therapy (or oral bisphosphonate therapy if intravenous is not available). If a child has significant potential for spontaneous reclamation of BMD and reshaping of vertebral bodies, the child can be monitored until resolution of risk factors and affirmation of recovery.

Figure 10

Children with osteoporosis should be treated with bisphosphonate therapy at published doses and in specialized centers by practitioners with experience in the care of such children.

Figure 11

This figure provides an algorithm for the treatment of osteoporosis with intravenous bisphosphonate therapy, the standard of care, including initiation doses (during the stabilization phase) plus dose titration (during the maintenance phase).