Given the number of confounding conditions evident in OI, a multidisciplinary approach involving pediatricians, surgeons, physical therapists, nutritionists, and even parents and educators is the most effective way to manage the disease in children and adults [13]. Fracture management and protection are the mainstay of OI treatment. To prevent immobility-induced bone loss following a fracture, casting is recommended for only the short term, to be replaced by splints and braces that can be removed to permit appropriate physical therapy. The need to avoid twisting, jolting, and jarring movements is of paramount importance, underlying the value of water therapy and swimming which offer a gravity-free environment to reduce fracture risk. Coupled with water activities, hip extension and hip abduction exercises, walking, dancing, bicycling, and weight lifting, if permitted, can help promote maximum bone density and decrease muscle atrophy [14, 15].

In children with OI, physical activity and an appropriate diet are essential to prevent obesity, which results in less movement and places added stress on bones. Adequate amounts of calcium to help prevent bone loss, vitamin D to promote calcium absorption, and vitamin C to ensure healthy connective tissues are also recommended. Smoking and excess alcohol consumption that can result in falls and fractures should also be avoided although primarily relevant in older teenagers.

Surgical interventions are generally unnecessary in type 1 OI. However, if severe bone deformities or serious fractures are present, surgeons are able to insert metal rods into the long bones of the legs to reduce fracture risk. Using the Fassier-Duval Telescopic Intramedullary System designed for OI patients who are still growing, a rod is attached on the far end of each growth plate and telescopes as the bone grows, overcoming the fracture risk posed by older rods with a fixed length [16].

In recent years, research studies on the treatment of osteogenesis imperfecta and osteoporosis have focused increasingly on drug therapy and particularly on the role of bisphosphonates as antiresorptive medicines that reduce the rate at which osteoclasts remove the bone and thus prevent the loss of bone mass. Clinical trials on the effectiveness of bisphosphonates have focused on children with severe OI, but some have been expanded to encompass those who are mildly or moderately affected. Studies incorporating patients with type 1 OI indicate that although bisphosphonate use is not recommended for the group as a whole, it may have individualized benefits for patients with repeated fractures and low bone density findings. For example, in a study of intravenous pamidronate (the most commonly used bisphosphonates for OI), Zacharin and Kanumakaia reported improved bone quality, increased mobility, and reduced fracture occurrence in children with less severe OI [17].

Other trials involving a range of OI types and other bisphosphonates such as IV ZA and oral alendronate show promising results [18, 19]. Although no bisphosphonate is FDA approved as OI therapy for children, “off-label” bisphosphonates are increasingly becoming the standard of care in children with moderate to severe forms of OI, reflecting demonstrated positive effects ranging from increased BMD and enhanced vertebral height to pain relief and greater muscular strength and mobility [20]. However, concerns have been raised about both the efficacy of bisphosphonates in reducing fracture risk and the duration of their use in children. Citing the results of several recent studies [21–23], Brizola and Shapiro warn that despite positive results from individual studies, an overall analysis of numerous trials reveals no clear consensus on whether bisphosphonates consistently decrease the incidence of fractures in children or adults with OI, nor is there evidence to address the concern that continued long duration treatment may adversely affect bone [24].

Within the last few years, a series of new investigations have been published, further elucidating the effect of pharmacologic interventions in OI. In a systematic analysis of the clinical, biochemical, and radiological outcomes of ten studies involving only children, Rijks et al. found that six trials indicated a significant reduction in relative fracture risk as a result of bisphosphonate therapy, with the optimal duration of such therapy still unclear [25]. In an effort to assess long-term treatment outcomes with bisphosphonates (pamidronate/ZA), Palomo et al. reported that 37 children who began bisphosphonate therapy (pamidronate/ZA) before age five and were close to or at final height at the time of the study had increased Z-score for LS BMD and taller stature but still sustained frequent fractures of long bones and developed progressive scoliosis, underlining the role of bisphosphonates as an adjunct treatment [26].

Beyond bisphosphonates, the positive effects of other medications on OI, including combination therapies such as recombinant growth hormone plus bisphosphonates, have been examined. Moreover, the first prospective clinical trial of denosumab in OI children has demonstrated a mean relative change in LS BMD of +19 % and bone resorption suppression for a duration of 10–12 weeks, indicating that denosumab should be safe in a 1-year treatment regimen with calcium and vitamin D supplementation. The effect of denosumab on fracture occurrence and the optimal duration of treatment are yet to be assessed [27]. Greater understanding of the mechanisms underlying OI holds promise of developing novel molecular therapies through infusion of mesenchymal stem cells [28].

Beginning in childhood, patients with OI should be taught to assume responsibility for themselves and to achieve as much independence as possible, given the severity level of the disease. Although generalized transition programs exist, they cannot encompass all the variable conditions associated with OI, underlying the need for approaches tailored to the medical condition and preferences of individual adults [29]. Critical to the transition is the continuity of medical care between pediatric and adult physicians and between physicians with limited knowledge of OI care and those with greater experience [30].

Clinicians must be aware of the confluence of conditions directly associated with OI and those affecting otherwise healthy aging adults, recognizing that, to a certain extent, the treatment for both may be the same. A decline in bone density can be related to immobilization from casts and lack of weight-bearing exercise as well as to age-related changes in the skeleton and hormonal system; however, symptoms of bone loss may appear at an earlier age than seen in people without OI. Periodic bone densitometry tests are recommended to identify osteoporosis, determine fracture risk, and monitor response to prescribed treatment. A healthy lifestyle, appropriate weight, adequate calcium and vitamin D through foods or supplements, smoking abstinence, limited alcohol use, and a safe exercise program, particularly aquatic therapy, will benefit patients with most types of OI. Those with type 1 may also be able to engage in noncontact sports that do not involve extensive twisting. Because they contribute significantly to bone loss, corticosteroids should be avoided [14].

Although fracture risk is known to decline following puberty, OI is a connective tissue disease, and adult patients with mild or moderate OI, particularly those with excessive joint flexibility, are likely to experience more soft tissue injuries as they age [30]. Impaired connective tissue can, in turn, lead to fractures as well as tendon, ligament, and muscle injuries and severe pain.

Bisphosphonate treatment has been studied in OI adults but to a more limited extent than in children and, thus far, with fewer positive results regarding fractures. Two studies of adult OI considered in a Cochrane review [21] revealed conflicting results. Although Adami et al. [31] reported a 14 % reduction in fracture incidence following treatment with IV pamidronate, further analysis of a subgroup of Adami’s subjects who had incurred at least one fracture [21] demonstrated no difference in fractures between these patients and controls. In a study involving alendronate, Chevral et al. [32] indicated no difference in vertebral or peripheral fracture rates. Both trials showed a significant increase in bone density.

Since 2010, additional studies of bisphosphonate treatment of OI in adults by Pavon de Paz et al. [33], Shapiro et al. [34], and Bradbury et al. [35] all reported an increase in BMD, but the results for fracture rate reduction were inconclusive. Shapiro indicated that while bisphosphonates did not decrease fracture rate in type 1 OI, IV pamidronate did lead to fracture reduction in more severe forms of the disease; Bradbury’s meta-analysis found no significant difference in fracture incidence in OI patients with oral bisphosphonates. At this point, insufficient evidence in support of the efficacy of bisphosphonates in reducing fracture rates does not justify a recommendation for general use, particularly over the long term when antiresorptive treatment has been associated with increased risk of atypical femoral fractures in OI patients [36]. Since there is such growing controversy in this area, expect to see more individualized approaches to treatment of patients with OI in terms of initiation of bisphosphonates.

The first trial examining the effect of the anabolic agent, teriparatide [37], on adult OI has produced positive results for type 1 in terms of increased hip and spine aBMD, vertebral vBMD, and markers of bone formation; efficacy was attenuated in more severe types 3 and 4. Larger trials are needed to evaluate teriparatide’s ability to reduce bone fractures in OI as well as to compare its effectiveness with that of bisphosphonates and other anabolic agents and when used in combination with other antiresorptive treatments. Several new therapies requiring further investigations have the potential to benefit patients with OI; they include cell-based therapies including bone marrow transplantation and gene therapy that focus on silencing, decreasing, or replacing the allele carrying the causative variant, effectively transforming a severe type of OI into a milder form of the disease [38, 39].

As adults age, the effects of adult OI are likely to be compounded by age-related osteoporosis. For the present, patients with OI, particularly type 1 combined with osteoporosis, must rely on the most promising pharmacologic treatments as well as nonpharmacologic interventions including good nutrition, adequate amounts of calcium and vitamin D, physical therapy to strengthen muscles, and occupational therapy to address educational, work, and ADL needs.