Management Of Osteogenesis Imperfecta In Adolescents And Adults

David Sillence (Connective Tissue Dysplasia Service)
New Children's and Westmead Hospitals, N.S.W., Australia, 2145.

As we enter the twenty-first century, more must be done to ensure that adolescents and adults with Osteogenesis Imperfecta have access to comprehensive management including assessment, medical treatment, rehabilitation and information resources about their disorder. In our centre, we provide such a service for children. While individualised for each child, the service otherwise involves the same core management offered to every child, i.e., there is a protocol. Why doesn't this happen for adults? Basically, services for adults are either not provided on a multidisciplinary basis, or adults must access a large number of linked specialty services which are neither integrated nor orchestrated. Hence the central objective for adolescents and adults with OI is to link in with a family doctor, general physician or rehabilitation specialist (all generalists) who is willing to coordinate their care and can be educated about OI and each OI adult's specific problems. The doctor will need to go on 'learning' about OI during this time. Childhood represents a fifth of life. So this 'generalist' will need to coordinate and orchestrate care during four-fifths of the life span: during adolescence, young adult life, post-menopausal/early aging period through to late aging. There are two broad categories of management themes, (i) continuous threads, (ii) age-specific management issues. Even people with 'mild' OI have numerous challenges with activities of daily living (ADL). The age-independent management issues include fractures, joint hypermobility, 'mobility', workplace accessibility and adaptation, and home adaptation.

Fractures do not 'cease' at puberty. Bone fragility persists throughout life. Fracture frequency may increase again after immobility or relative inactivity and during or following childbirth in women. It increases dramatically in middle age in people with OI either in the post-menopausal period or in men in the fifth to sixth decade. Fractures take longer to heal (approximately four times as long as in childhood), sometimes don't heal (non-union) and may pose special orthopaedic challenges.

Joint hypermobility particularly in fingers and wrists presents very special challenges. These can be overcome with soft wrist and metacarpo-phalangeal joint supports, various aids to assist grip and a soft keyboard or electronic note-taker.

Osteoporosis is the number one issue. Adults with OI have osteoporosis for many reasons. They are usually osteoporotic because they entered adult life with osteoporosis in childhood which resulted from decreased bone synthesising ability during growth, immobilisation due to recurrent fractures, or reduced physical activity, i.e., decreased stimuli to increased bone formation. In adult life, fractures may re-occur, people may be too busy to exercise regularly and calcium intake may be poor. While OI is not a calcium problem, osteoporosis is definitely aggravated by poor calcium and protein intake. It is so simple to prevent. Calcium-rich foods include all 'reduced fat' milks, yoghurts and cheeses. Adults need between 800 mg and 1200 mg of elemental calcium per day every day.

What can be done? Each adult with OI should have regular bone densitometry. This could be every 3-5 years between 20 and 35-40, but if there are significant life events which contribute to osteoporosis, perhaps yearly. After 35 in females, and 40 in males, bone density might be performed annually. If this is performed regularly at the one centre the measurements are extraordinarily reliable and serial measurements are particularly valuable. Symptoms of symptomatic osteoporosis, including unusually easy tiring, weakness, bone pain (particularly back or hip pain), can be assessed and treated.

Treatment of osteoporosis. In 1999, there are no clear guidelines about which drug, when and for how long. However, if enough adults work with the centre, it might be possible to answer these questions. For example, post-marketing experience with the anti-resorbtive bisphosphonate Alendronate has demonstrated a high frequency of gastro-intestinal side effects, some of a serious nature. However, other bisphosphonates, cyclic IV Pamidronate, Risedronate and Zoledronate are being trialled in various centres. If we recruit significant numbers into treatment trials, we could answer the questions about efficacy and safety very quickly.

Pregnancy related issues. Many women with OI seek genetic counselling. However, the major issue is that each baby selectively takes its skeleton from its mother. During the last trimester and early breastfeeding, about 6 % of the mother's bone mass is transferred to her baby. Women with OI who have not had fractures for years commence having vertebral crush and even long bone fractures. Furthermore, without careful monitoring and treatment these women never restore their bone density to pre-pregnancy levels.

Post-menopausal and age-related osteoporosis. Until recently, post menopausal bone loss seemed to be inevitable, foreshadowing an increase in fracture frequency and morbidity in women in the fifth decade. However, there are at least four major alternatives for women at this time of life, several of which are complementary (i) increased regular weight-bearing exercise, (ii) conjugated oestrogens, (iii) selective estrogen receptor modulators, SERMs, (iv) anti-resorbtive drugs such as bisphosphonates (see previously). For males there is similarly the promise that bone loss can be prevented or minimised by a combination of (i) and (iv).

Understanding as much as we do, there has never been a previous time when there was such opportunity to improve the quality of life for adults with OI. Specific programs for prevention and treatment of osteoporosis can be combined with annual health checks which include the diagnosis and treatment of all the health issues appropriate for the person's age, as well as OI-related complications including Obstructive Sleep Apnea, Basilar Impression, floppy mitral valve, and progressive conductive hearing loss (mainly in OI type I). All that is needed is for adults to work together to support centres of excellence in OI care in their role of informing the generalist family practitioners about specific OI related issues and their management.

Reference: Proceedings of the 7th International Conference on Osteogenesis Imperfecta. Montreal, Canada, 1999.