A diagnosis of OI should be considered in any child with recurrent fractures from minimal trauma [3]. Family history, clinical examination, and radiological findings are important for diagnostic confirmation. The clinical picture is not always characteristic. Extra-skeletal manifestations may be subclinical (hearing loss), nonspecific, or more common at some ages (dentinogenesis imperfecta is most notable in the first dentition).

Child victims of trauma, as well as patients with severe OI, may exhibit multiple fractures at different stages of fusion. In a study involving 39 children (older than 1 year of age) with fractured collarbones, 82 % were considered to be the result of child abuse, 8 % accidental injury, and 8 % bone fragility, and in one case fractures were the result of osteogenesis imperfect itself [12].

Another study evaluated 61 children victims of child abuse. After reviewing the medical records, 33 cases were confirmed as OI. The median age at examination was 7.1 months. All patients had fractures, 14 exhibited pain, 7 swelling, 5 showed limited movements, and 2 showed an abnormal position of their limbs. Radiographic findings consistent with OI were found in 19 of 33 patients (58 %); clinical findings were present in 23 of 33 patients (70 %), and a family history of OI in 55 % [13]. Therefore, in cases where child abuse is suspected, OI should always be considered, since any error in diagnosis can lead to serious consequences for the children and their families.

The clinical picture of OI is not always characteristic. Patients with mild OI exhibit no fractures until they start to move around. Retinal hemorrhage, subdural hematoma, and bruising may also occur as indirect signs of trauma.

Rickets may cause slow growth, bone deformities, elevated alkaline phosphatase, defects in bone mineralization, and, in some cases, abnormal formation of the teeth. Abnormalities in the sclera and hearing loss typically do not occur and on X-rays, epiphyseal plate enlargement is present. In the adult patient, osteomalacia may cause bone pain, fractures, and elevated alkaline phosphatase, also without causing hearing loss or blue sclera. Radiological findings include decreased bone density, pseudofractures, and loss of trabecular definition.

Other rare skeletal syndromes causing bone fragility and deformities should also be considered in the differential diagnosis of OI and these include Bruck syndrome, osteoporosis pseudo-glioma syndrome, polyostotic fibrous dysplasia, and juvenile Paget’s disease, hypophosphatasia, and idiopathic juvenile osteoporosis.

The focus of treatment should be multidisciplinary in order to oversee early care and minimize complications. The objective is to reduce the rate of fractures, prevent deformities, decrease chronic pain, and improve functional capacity.

Bisphosphonates are the main therapeutic agents used to prevent fractures in most forms (except for type VI) although none have been approved specifically for use in children and adults with OI. Bisphosphonates are stable pyrophosphate analogues, and are potent inhibitors of bone reabsorption and bone turnover.

The majority of studies was conducted in children and did not include control groups. Observed benefits included an increase in bone mineral density, reduced fracture rate, and improvement in mobility and pain [14]. Pamidronate is administered intravenously during consecutive 3-day cycles, with 2–4-month intervals, using 0.5 mg/kg/day up to 1 mg/kg/day depending on the age (Table 26.3).

Short-term adverse effects on bone quality and fracture healing are not present, despite the significant reduction in bone turnover with bisphosphonate treatment [15]. Linear growth does not appear to be affected and the greatest benefit seems to occur within the first 2–4 years of therapy. It is prudent to reserve pamidronate for patients in whom the clinical benefits outweigh the risks (deformity of long bones, vertebral compression fractures, and three or more fractures per year) since the long-term effects as yet are not well understood [16].

In a meta-analysis, oral risedronate (35 mg per week) for 24 weeks led to bone mineral density increases by 3.9 % at the lumbar spine without statistical significance in the total hip measurements. Bone pain did not improve significantly, and the fracture rate remained high [17].

In most cases, orthopedic care focuses on fractures, but also should be considered for the correction and prevention of deformities, especially in the lower limbs, including surgical treatment.

Osteomalacia is not a common metabolic bone disease, but is often neglected especially in its early stages because of the nonspecific nature of symptoms such as vague bone pain and muscle weakness [18]. The disease is characterized by a generalized weakening of bone, leading to deformity, and it is often caused by defects occurring at any step of the metabolism or action of vitamin D [19]. It occurs mostly due to dietary deficiency and exposure to sunlight, but can also be due to intestinal malabsorption, chronic kidney failure, or vitamin D resistance [18] (Table 26.4). Osteomalacia can also occur in patients with primary hypophosphatasia (Table 26.5) due to one of the syndromes of hereditary hypophosphatemia (X-linked, autosomal dominant and with hypercalciuria) or oncogenic due to fibroblastic growth factor-23 (FGF-23) secretion by the tumor [20, 21].

There is an increasing prevalence of vitamin D deficiency in many countries, even in those close to the equator, and those with abundant sunlight [22]. The at-risk population includes the elderly with little exposure to sunlight as well as patients with poor absorption including those with celiac disease and those submitted to gastrointestinal bypass surgery. Likewise, individuals living in cold weather climates, and women who wear clothes that cover almost the entire body area, are also predisposed to hypovitaminosis D [19].

The main histological findings are an excessive accumulation of bone matrix that is not, or only poorly, mineralized, decreased bone volume, increased accumulation of osteoid, and increases in the osteoid thickness of bones and the surface area [23].