Evaluation and Management of Osteoporosis in Individuals with Developmental Disabilities

Introduction It has been estimated that over 50% of women and 12% of men will suffer an osteoporosis related fracture in their lifetime. The medical costs associated with osteoporosis related fractures are in the many millions of dollars while hip fractures in the elderly are fatal in 1 out of 5 cases.

It is not surprising, therefore, that medical scientists and health services policy makers as well as the lay press, have focused on osteoporosis as a major health hazard in the United States and the world.

Since osteoporosis is an "aging-related" condition it is ironic that success in public health policy and medical sciences which have led to improved longevity will also lead to an increasing incidence of osteoporosis related conditions such as spontaneous fractures and kypho-scoliosis (which may be complicated by chronic cardio-pulmonary failure).

While osteoporosis is often viewed primarily as a "women's health issue," it is also prevalent in other populations as well, especially the elderly of both sexes and people with disabilities associated with immobility, regardless of their age or sex.

Diagnosis of Osteoporosis Osteoporosis is usually defined as a reduction of bone mineral density per unit volume of bone. Strictly speaking osteoporosis is caused by reduced bone "matrix" (the organic component of bone), while "osteomalacia" is caused by reduced mineral deposition secondary to Vitamin D deficiency. Some use the term "osteopenia" to refer to an early form, before frank osteoporosis has occurred. For practical purposes, the term "osteoporosis" is used to mean reduction of bone mineral content (density) which is detected by routine X-rays or bone densitometry. Bone densitometry is the preferred method of diagnosis because osteoporosis must be severe before it can be detected by routine X-rays. Dual-energy X-ray absorptiometry (DEXA) is the "gold standard" for determination of bone mineral density (BMD). Usually DEXA is performed at two sites, the hip and the spine. BMD is usually expressed as a "range' compared to a normal population because the BMD cannot be directly compared between various sites. Thus, the results are commonly expressed in relation to a young-normal standard deviation (T-Score) and/or an age-matched standard deviation (Z-Score). The World Health Organization has defined osteoporosis as a BMD T-Score of greater than 2.5 Standard Deviations below the mean for a young-normal population. People with BMD values between 1 and 2.5 Standard Deviations below the mean for a young-normal population are said to have "osteopenia." Individuals with osteoporosis defined in this way are at high risk for fractures, while individuals with osteopenia are at risk for osteoporosis and should be treated.

Evaluation of Osteoporosis in People with Developmental Disabilities There is little medical literature which addresses the problem of osteoporosis in people with disabilities. Larin, et. al, determined BMD by DEXA in 6 children ages 3-5 years, with spastic diplegia, and found DEXA to be a reliable method for determination of BMD.

Lin and Henderson (1996) using DEXA examined the BMD of the extremities of 19 children with spastic cerebral palsy and found the BMD of the affected limbs to be significantly lower than the BMD of the more functional extremity. The authors suggested that reduced purposeful movement leads to less "stress" on bone which is necessary for normal bone mineralization.

Wagemans et. al., (1998) performed DEXA on 23 bedridden adults with mental retardation and found osteoporosis in 61% in spite of adequate dietary intake of Calcium and Vitamin D.

Quan et. al., (1998) screened for osteoporosis in 35 children with myelomeningocele ages 6-19 years by measurement of bone mineral density of the distal radius. Biochemical markers of bone metabolism (pyridinoline cross-links) were also determined in this study. The authors found that BMD for the group (Z Scores) was significantly below the mean for the age-matched normal population and that the BMD of the 8 patients who suffered multiple fractures was significantly below that of the 27 patients who were fracture-free. In addition, elevated biochemical markers (cross-links) were more frequently elevated in those individuals with the most impaired mobility. The authors concluded that individuals with myelomeningocele have an increased risk for spontaneous pathologic fracture because of reduced bone mineral density secondary to immobility and that measurement of BMD and biochemical bone markers may help to identify those patients who are at greatest risk for fractures.

Ehrenkranz and May, (1993) examined the relationship of estrogen deficiency and osteoporosis. They determined the incidence of abnormal menses in 212 females with profound mental retardation ages 22-59 years. The incidence of reduced or absent menses was found to be 3 times higher in the young (less than 40 yrs.) group with mental retardation as compared to the normal population. Reduced BMD was demonstrated in this group suggesting that estrogen deficiency in the young female with mental retardation is a "risk factor" for osteoporosis, as it is in the post menopausal female.

In a related study at a Developmental Center, using an "Injury Risk Assessment" instrument in a population of 650 individuals, 117 were found to be at moderate risk and 42 at high risk of fracture from osteoporosis.

All of these studies suggest that risk of fractures from osteoporosis is a significant problem in people with disabilities regardless of age and sex, although age and sex are additional significant variables. It appears that immobility is the most significant risk factor for osteoporosis (and fractures) in people with developmental disabilities. The mechanism of immobility-induced osteoporosis is related to the reduced piezo-electric (pressure) stresses on bones which is in turn secondary to neuro-motor dysfunction. In addition, our studies have demonstrated that gonadal dysfunction is more prevalent in both woman and men with developmental disabilities and this may be an additional unique risk factor in this population. Diminished gonadal function is secondary to various genetic gonadal hypothalamic conditions such as Kallman's Syndrome, Prader Willi Syndrome, Septo-Optic Dysplasia, Kleinfelter's Syndrome and Turner's Syndrome. In addition, since growth-hormone deficiency may cause osteoporosis, (e.g., Prader Willi Syndrome, Septo-Optic Dysplasia), hypothalamic deficiency may lead to osteoporosis by multiple mechanisms.

Causes of osteoporosis that are common in the aging general population (i.e., post-menopausal and geriatric) are of course present in older adults with developmental disabilities as well. However, rarely are these "usual" causes the only causes and it is imperative that other etiologies be considered as well. These would include immobility, hypothalamic and gonadal failure as discussed above and also toxicity from drugs such as Dilantin which interfere with Vitamin D metabolism.

Rare causes of osteoporosis that should be ruled out in any population with demineralization are hyperparathyroidism, Cushing's Disease, Homocystinuria, Lowe's Syndrome and other causes of renal tubular acidosis, intestinal malabsorption syndromes, Vitamin C deficiency, and hyperthyroidism.

Prevention of Osteoporosis It has been convincingly demonstrated that adequate intake of calcium (1000-1500 mg/day) and Vitamin D (400 units/day) with regular exercise can help prevent osteoporosis in the general population. In addition, hormone replacement therapy (HRT) with estrogen can help prevent osteoporosis in post-menopausal women if initiated soon after menopause.

How this information applies to people with disabilities with complex medical problems is not at all clear, but it would be reasonable to assume that diet and exercise are important (but probably not sufficient) adjuncts in the prevention of osteoporosis in people with disabilities just as they are in the general population.

Without minimizing the importance of efforts to prevent osteoporosis in people with developmental disabilities, the fact remains that many disabled people with complex conditions associated with mobility disorders have advanced osteoporosis which puts them at risk for sudden spontaneous fracture. It is important that this group be treated.

Treatment of Osteoporosis Ideally, osteoporosis that has not been prevented, should be treated. Treatments that are available include diet, exercise and drugs. Drugs include alendronate (Fosamax), etidronate (Didronel), thyrocalcitonin (Calcimar, Miacalcin), Estrogen (e.g., Prempro) in women, and Androgen (e.g. Halotestin) in males. Selection of one or more of these modalities currently depends on the clinical judgement of the prescribing physician. Since medical literature which demonstrates efficacy of treatment of osteoporosis in people with severe developmental disorders is virtually non-existent, it will be necessary to monitor efficacy of treatment on an individual basis. A baseline measure of osteoporosis should be determined before treatment is started (e.g., DEXA, and/or pyridinoline cross-links) and then repeated at periodic intervals (perhaps yearly) to demonstrate that bone mineral density is increasing (or at least not getting worse). Documentation of efficacy should be a standard of care whenever a patient is exposed to a potentially toxic drug and this principle should certainly apply to the treatment of osteoporosis. Summary and Conclusion Osteoporosis is common in people with severe developmental disabilities, young and old. males and females. Those factors in the general population that correlate with osteoporosis (aging and estrogen deficiency) should be considered in children and adults, males and females with disabilities as well. Programs designed to prevent and/or treat osteoporosis in the general population may not be efficacious in people with developmental disabilities. It will be important to develop clinical protocols designed to determine which prevention and treatment regimens will be safe and effective in people with disabilities. Without performing this "medical homework" we will not be able to determine optimal standard of care for individuals with developmental disabilities who are at risk for osteoporosis.

Selected References

1. Lin P., Henderson R. Bone Mineralization in Children with Spastic Hemiplegia. Developmental Medicine and Child Neurology 1996,38, 782-786

2. Wagemans A, et al. Osteoporosis and Intellectual Disability: Is there any Relation? J. of Intellectual Disability Research 1998,42, 370-374.

3. Quan A., et al. Bone Mineral Density in Children with Myelomeningocele. Pediatrics 1998,102, p e 34 (electronic article)

4. Van der Reis, W. Femoral Neck Fracture in a Young Man with Hypogonadotropic Hypogonadism: A Case Report. Resident and Staff Physician 1998,44, 84-87

5. Jancar J. Age Related Fractures in People with Intellectual Disability and Epilepsy. J. of Intellectual Disability Research 1998,42, 429-433

6. Ehrenkranz, J. and May P. Oligomenorrhea and Osteoporosis in Women with Mental Retardation. Endocrine Society Abstracts, 1933, Abstract 1032, p308.