When focused on pediatric patients with T1D, measurements of bone mineral density by dual X-ray absorptiometry (DXA) alone have provided conflicting results [20], with specific reports demonstrating global reductions in BMD [68], site-specific reductions in BMD [69, 70], or minimal to no effect on bone density [71, 72]. By providing only a two-dimensional estimate of BMD, however, DXA neglects parameters of bone size, bone geometry and bone compartment, which are critical components of the integrity of the growing skeleton. Other investigations using QUS or peripheral quantitative computed tomography (pQCT) provide additional information on bone mineral content, bone size, and bone structure. Collectively, these studies do suggest that cumulative changes in bone architecture are beginning early in childhood, particularly in those diagnosed with T1D at very young ages [73]. Compared with nondiabetic children, reductions in BMD [68, 74–78] and bone size, specifically total cross-sectional area (CSA) [73, 79] and cortical area [15, 80], are relatively consistent findings. Consequently, total bone mineral content of these generally smaller bones is also reduced in pediatric patients with T1D [80].

A mild delay in skeletal maturation, acquired after diagnosis, has been reported in some studies [81, 82]. In addition, the age of peak bone mass acquisition may be delayed in individuals with T1D [68, 72] and chronically poor glycemic control may negatively impact growth velocity [83]. However, unlike historical reports of short stature (i.e., Mauriac syndrome) in poorly controlled T1D [84], in the modern era of tighter glycemic management the impact of T1D on final height is minimal [73, 82, 85].

As with adults, the impact of T1D on the pediatric skeleton may again be gender-discrepant. Several studies report a more significant impact in young males [80]. Additionally, in a study of females, 13–19 years of age, no differences in BMD, measured by DXA, were seen when comparing T1D with control subjects [72]. Other comorbidities, including the diagnosis of associated autoimmune disorders during childhood [86], may also exacerbate the impact of DBD on the growing skeleton (see section “Effects of Ancillary Diagnoses: Celiac Disease, Autoimmune Thyroid Disease, Addison’s Disease”). Possible pediatric risk factors for DBD are listed in Table 1.2. Evidence to date would suggest that in patients with one or more of these risk factors, earlier screening for DBD may be warranted.

The relationships between autoimmune disease and bone loss are multifactorial, with outcomes dictated by: (1) direct immune cell regulation of bone homeostasis; (2) disease-specific systemic or local inflammation (e.g., rheumatoid arthritis); (3) disease-specific systemic hormone alterations (e.g., hypothyroidism/hyperthyroidism); (4) ancillary organ damage; or (5) negative skeletal consequences of therapy (i.e., corticosteroids) (For Review, [145]). Certain autoimmune disorders in particular, including autoimmune thyroid disease (ATD), celiac disease (CD), and Addison’s disease (AD) are more prevalent in persons with T1D, and all can independently confer detrimental effects on skeletal homeostasis, compounding the impact of diabetic bone disease. The prevalence of celiac autoimmunity or CD in persons with T1D has been estimated at between 4 and 12 % [86, 146–149] and osteoporosis, along with an increase in the risk of bone fractures, is present in the majority of celiac patients [150]. It is interesting, therefore, that in children with T1D, high-titer seropositivity to celiac antigens in otherwise asymptomatic children is associated with lower bone mineralization [151]. Similarly, in studies of BMD in adults with T1D, a greater reduction in BMD, as well as a higher incidence of fractures [149], is seen among the subset of T1D patients with concurrent celiac autoimmunity [149, 152, 153]. In patients with T1D and active CD, a significant increase in the prevalence of osteopenia (compared to T1D alone) is seen in those with seropositivity and non-adherence to dietary gluten restrictions [154]. Finally, autoantibodies against osteoprotegerin have been reported in a few patients with celiac disease, possibly further contributing to osteoporosis [155]. Hence, in persons with a long-standing coexistence of T1D and CD, the risk for poor bone health is almost undoubtedly higher.

Autoimmune thyroid disease (ATD), either Hashimoto’s disease or Grave’s disease can occur in 12–30 % of persons with T1D [86, 147], likely related to a common genetic susceptibility for the two disorders [156]. Whether related to the primary hormonal disruption, or to the antithyroid autoimmunity [157], these thyroid disorders can independently contribute to a decrement in BMD. Prevalence rates for adrenal autoantibodies and/or Addison’s disease (AD) among persons with T1D vary from 0.5 to 1.4 % [86, 147, 158]. While Addison’s disease is a rare condition, AD is also associated with a higher prevalence of osteopenia or osteoporosis [159] and an increased risk of fracture [160], which is unrelated to glucocorticoid replacement therapy. At present, it is not clear whether the diagnosis of ATD or of AD in a person with T1D further increases the risk of osteoporosis or fracture; however, the combination of multiple autoimmune diseases in some persons with T1D may synergistically increase the risk of low bone mineral density [29].

Because diabetic bone disease in type 1 diabetes represents a deficit in osteoblast function and bone formation, antiresorptive therapies for osteoporosis (e.g., bisphosphonates, denosumab) may be ineffective in this form of secondary osteoporosis, other than as combination therapy in conditions of increased bone resorption (i.e., postmenopausal females with T1D) [161]. Calcium and vitamin D supplementation, where indicated, is considered standard-of-care for osteoporosis treatment [162]. Nonetheless, 1 year of calcitriol supplementation in young adults with recent-onset T1D did not significantly change circulating markers of bone turnover, specifically levels of OC or beta-Crosslaps [160]. Moreover, very little information from comparative effectiveness studies is available on the treatment of osteoporosis in T1D. In animal models, intermittent PTH treatment has been shown to improve osteoblast survival and reverse diabetes-associated bone loss [163]. In clinical trials examining the effectiveness of injectable PTH (teriparatide) for treatment of osteoporosis, however, diabetes has typically been an exclusion criteria preventing enrollment, though positive results with off-label use of teriparatide for nonunion fracture repair [164] or Charcot osteoarthropathy provide some early support for this concept. Clearly, additional clinical investigation in this area is needed.

Greater than 90 % of peak adult bone mass is typically achieved by the end of the second decade of life, and ~40 % of this bone mass is acquired during the adolescent growth spurt; hence, adolescence is a period of particular importance for prevention strategies. Optimal T1D disease management in children and adolescents, according to best practice guidelines [3], would seem a prudent approach to minimizing the impact of T1D on skeletal tissues. This would include effectively managing blood glucose to achieve age-appropriate treatment goals for plasma glucose and HbA1c, as published [3]; additionally, adequate insulin replacement may, in and of itself, have beneficial anabolic effects on bone [20]. Routine screening for associated autoimmune disorders, such as celiac disease and hypothyroidism, as is recommended, is also a necessary component to prevention [3].

Optimal bone mineralization during puberty should also become an important objective for the pediatric clinician, utilizing the following general guidelines:

The FRAX^® tool, or World Health Organization Fracture Risk Assessment tool, was developed to integrate BMD measurements and patient-specific clinical risk factors in determining an individual’s 10-year probability of fracture. Current American Diabetes Association (ADA) Standards of Medical Care for fracture assessment are largely derived from studies of fracture risk in type 2 diabetes, which suggest that for a given FRAX^® score, the risk of fracture is higher in persons with diabetes [3, 173]. ADA guidelines state that “it is appropriate to assess fracture history and risk factors in older patients with diabetes and recommend BMD testing if appropriate for the patient’s age and sex” [3]. Additionally, the fracture risk prediction algorithm used in the United Kingdom (QFracture algorithm) has been recently updated to incorporate type 1 diabetes as a specific variable in their hazard assessment [174]. Guidelines for BMD testing in children and adolescents with T1D, however, do not currently exist.

Persons with type 1 diabetes, particularly those with long-standing disease, are at significantly increased risk for osteopenia or osteoporosis, fractures, and poor bone healing, collectively now termed diabetic bone disease. Many factors contribute to these deficits in skeletal integrity, including: (1) a disease-specific reduction in new bone formation; (2) an increased occurrence of vitamin D insufficiency; (3) a variety of bone-adverse comorbid conditions, including diabetic microvascular complications and associated autoimmune diseases; and, very possibly (4) glucose-related alterations in the material properties and mechanical strength of diabetic bone. Because T1D is most commonly diagnosed in childhood and adolescence, the early assessment of bone health and skeletal risk factors in youth with T1D will be important, in an effort to maximize the acquisition of peak bone mass in these patients, and to minimize the impact of T1D on the skeleton going forward.