Skeletal and extraskeletal characteristics of rare bone disorders with special focus on osteogenesis imperfecta

In chapter 2 an overview of the Dutch OI population was given. 724 OI patients were identified between 1991 and 2021, estimated to be 85% of the total Dutch OI population.The median annual incidence of OI was 6.5 per 100,000 live births. These patients had a 2.9 times higher hospitalization rate compared to the general Dutch population. The highest hospitalization rate was reported in the patient group 0-19 years. Admissions to the departments of pediatrics, surgery and orthopedic surgery were the most prevalent. In chapter 3 ocular characteristics and complications in OI were studied by a systematic review of the literature. This systematic review showed that almost every component of the eye could be affected by the disease as a result of alterations in collagen type I. A decreased thickness of the cornea and sclera was an important underlying factor in several eye conditions. The most common eye condition in OI is blue discoloration of the sclera. Findings that stand out were ruptures, lacerations and other eye problems that occur after minor trauma, as well as complications from standard surgical procedures. In chapter 4 the auditory system of a mouse model for mild OI was studied to gain more insight in the pathophysiology of hearing loss. The morphology of the otic system was studied in ten wild type (WT) and ten Mov13 littermates at the age of eight weeks. No gross anatomical differences were found between WT and Mov13 littermates. Significantly higher vessel size was found in the Mov13 mice compared to WT mice. The Mov13 middle ear ossicles were mainly found to be composed of cartilage, while almost no cartilage remnants were found in the WT littermates. Three fractured ossicles were seen in Mov13 mice, compared to one fracture in the WT group. It can be concluded that the development of the Mov13 mice might be slower compared to their WT littermate. This may contribute to increased fragility of the ossicles and vascular differences in the otic capsule. In chapter 5 the pathophysiology of respiratory failure in patients with OI was investigated by a systematic review. Respiratory failure is a major cause of death in OI as well as it impairs quality of life. This literature review showed that pulmonary function disorders could be caused by scoliosis or thoracic skeletal deformities. A more interesting finding was that reduced pulmonary function could also be the result of a primary pulmonary problem due to intrinsic collagen alterations. Lung function deteriorates further when intrapulmonary defects are combined with severe thoracic abnormalities. In chapter 6 a systematic review identified a variety of advanced techniques for structural, material, mechanical and immunological characteristics of bone tissue. The broader use of bone material from biopsies could provide more information about the pathophysiology or best treatment options in rare bone disorders. These advanced techniques have only been used in research and not in daily clinical practice. Further improvements are required for the development of reference data, a cooperative network of researchers and clinicians and the availability of these techniques in more hospitals. In chapter 7 the case of a 34-year old patient with pregnancy and lactation associated osteoporosis was studied. She was treated with teriparatide (TPTD) and zoledronic acid (ZA) because of low BMD. DEXA and HR-pQCT were used for follow-up until forty months postpartum. Substantial improvements in BMD, microarchitecture, and strength were reported at the total hip, spine, distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA. Nonetheless, BMD, microarchitecture, and strength remained impaired in comparison with healthy age- and gender-matched controls.