BY PHILIP MAY MD
Prevention, Evaluation, and Management of Low Bone Mineral Density (BMD) Encountered in Adults with Developmental and Intellectual DisabilitiesClinical experience and published reports have shown that low BMD is especially common in adults with developmental disabilities, such as intellectual disability, epilepsy, autism, and cerebral palsy.
For various reasons, high frequency of low bone mineral density (BMD) and increased risk for fracture are often encountered in adults with “medically complex developmental disabilities” (MCDD). Treating physicians who wish to address these twin problems of low bone mineral density and increased risk for fracture discovered in their patients with MCDD should begin with a careful patho-physiological evaluation of his or her patient’s “bone health”, because, in
this “medically underserved population”, there exist multiple mechanisms that can lead to a lowered bone mineral density. Understanding the basic underlying patho-physiological mechanisms will guide the treating physician to select the most rational approach that will lead to the best clinical outcome of lowered risk for fracture. In addition, It should be emphasized that this patient population experiences multiple co-morbid health conditions that have competing effects on different organ systems; therefore, more complex therapy must be managed on an individualized person-centered basis and should not be dictated by algorithms that might be proper strategies for public health decisions.
Low bone mineral density (BMD) is commonly determined by Dual-Energy X-ray bsorptiometry (DXA). Clinical experience and published reports have shown that low BMD is especially common in adults with developmental disabilities, such as intellectual disability, epilepsy, autism, and cerebral palsy. Regardless of the cause of the developmental disability, low bone mineral density occurs in as many as 80% or more in some studies.1-3 Having low BMD increases the “risk” for fracture and, not surprisingly, the actual incidence of fracture in adults with developmental disabilities is increased as well.4 It should be underscored that there may be multiple pathophysiological mechanisms that lead to low BMD. For example, in post-menopausal women estrogen deficiency leads to increased osteoclastic activity over osteoblastic activity and this leads to overall loss of bone mass. On the other hand “Rickets” in children or “Osteomalacia” in adults is caused by vitamin D deficiency which leads to failure to mineralize osteoid.
In this case bone mass is normal (or even increased) but the bone is not properly mineralized (thus low BMD). In either case, postmenopausal osteoporosis or osteomalacia, the DXA machine will read “low BMD”. Of course the management of these two conditions is very different. Thus, understanding the underlying pathophysiology of the various causes of low BMD is critical to ensure good patient outcomes.
The causes of low BMD in adults with developmental disabilities include: 1) failure to obtain a normal peak bone mineral density during young adulthood, 2) lack of adequate regular weight bearing exercise, 3) immobility secondary to neuromotor dysfunction, 4) the adverse effects of various drugs (e.g. neuroleptics, SSRIs, lithium, antiepileptic medication, and proton pump inhibitors), 5) vitamin D or calcium deficiency, 6) aging osteoporosis and 7) post menopausal or and ropausal osteporosis.
During early childhood bone mass rapidly increases and peaks at approximately 15 to 25 years of age. Bone mass then plateaus from age 25 to 45. After age 45, in both men and women, bone mass begins to decline. The rate of this decline increases dramatically for women after menopause due to diminished estrogen secretion by the ovaries. For various reasons, many adults with MCDD fail to obtain a normal Peak BMD. Thus, these individuals become at greater risk for dangerously low BMD as they age after 45 years.
Bone is a dynamic tissue that is constantly renewing itself, a process known as “remodeling” (new formation and new breakdown occurring at various sites at different times). The rate of this “remodeling” depends on needs for calcium in the blood and also needs for mechanical support for the skeleton at specific sites that are undergoing mechanical stress. Remodeling depends on the interplay of two important bone cells: 1) the osteoblast that is responsible for bone formation and 2) the osteoclast which is responsible for bone resorption/breakdown. A third bone cell, the osteocyte, will be discussed below. There is an extensive network of osteocytes in bone that possess long “dendritelike” processes. It is believed that this osteocytic network serves as a type of “nervous system” that detects and responds to mechanical stress by stimulating osteoclasts and osteoblasts to remodel bone as needed. This “piezo(pressure)-electric” system of osteocytes may act on osteoclasts and osteoblasts independently of, or in addition to, the vitamin D and parathyroid hormone systems.
When an individual loses motor function and ability to bear weight (mechanical-unloading), the skeletal osteocytic network system activates osteoclasts to remove calcium from bone. Serum CTX levels increase and more calcium is delivered to the bloodstream. When mechanical unloading is an acute process hypercalcemia can occur. Increased calcium leads to suppression of PTH. Suppression of PTH leads to reduced renal formation of “active” vitamin D and less GI and renal calcium absorption. Suppression of PTH also leads to reduced production of new osteoclasts (via RANK ligand). In addition, “mechanical unloading” will activate the osteocytes to release “Sclerostin” which inhibits/destroys osteoblasts and therefore inhibits production of new bone.5 Thus, for a period of time following mechanical unloading, there is an uncoupling of bone turnover, against bone “formation” and in favor of bone “resorption”. Eventually, a new steady-state of “coupled” low bone turnover (formation and resorption) will be created. Thus, with long-standing paralysis (e.g. Cerebral Palsy), bone turnover may be low (low serum CTX and P1NP), and so will be the bone mineral density (BMD). Since low BMD increases the risk for fracture. It makes sense to treat this “condition” (Low Bone Turnover with Low BMD) with anabolic agents, such as teriparatide, rather than anti-resorptives, such as bisphosphonates and denosumab.
Thus, in persons with developmental disabilities with lifelong neuromotor dysfunction and a chronic state of low weight bearing mechanical stress on bones, the body “perceives” that a normal bone mineral density is “not needed”, thus a greater proportion of ingested calcium is used for purposes other than bone formation. When bone turnover is evaluated by measurement of serum P1NP (osteoblast) and CTX ( osteoclast), one will often find low normal levels because a chronic state of low bone turnover exists, in association with a low bone mineral density (BMD) on DXA. Special attention should be paid to the usage of psychotropic and seizure medications. Efficacy of these classes of drugs should be carefully documented and if they are demonstrated to not be absolutely necessary, they should be tapered and discontinued. Drug-Related Bone Loss (DRBL) is probably a major cause of low BMD encountered in adults with developmental disabilities, and efforts to eliminate polypharmacy may provide enormous benefits with regards to reduction in fracture risk in this special population of adults.
Optimization of vitamin D and calcium is another important strategy that has the potential to increase bone mineral density in adults with developmental disabilities. When maximally stimulated by the sun the skin has the capacity to produce 10,000 to 20,000 international units of vitamin D per day. Adults need approximately 3000 to 5000 units per day to support normal metabolic unctions (almost all cells have vitamin D receptors). During the winter months (October through April), 80% of the daily needs for vitamin D come from vitamin D (2400 to 4000 IU’s/day) that was stored during the summer months (May through September). Thus 20% (600 to 1000 international units/day) is needed to be supplied by the diet or supplements in order to avoid vitamin D deficiency during the winter months.
However, many people with developmental disabilities, especially those who reside in institutions, have little outdoor activity during the summer months and when they do have outdoor activities tend to be covered with sun block and clothing in order to prevent sunburn. Therefore adults with developmental disabilities most likely have very low stores of vitamin D and are at great risk for vitamin D deficiency especially during the winter months. Of course those who are in addition receiving drugs which interfere with vitamin D metabolism are at an even greater risk for vitamin D deficiency. In the process of optimizing vitamin D for adults with developmental disabilities, it probably makes sense to begin with a “loading” dose of vitamin D in order to replenish vitamin D stores. A common regimen that has been shown to be safe and effective is to begin with 50,000 international units of vitamin D3/ per week for 8 to 12 weeks, and then continue a maintenance dose of 50,000 units per month.6-8
There does not appear to be a universal agreement on the best target blood level but a 25 hydroxy vitamin D level of 40 to 50 ng per ML is probably reasonable.9 It should also be determined that hypercalcemia does not occur, and that bone turnover markers (P1NP and CTX) are not elevated. Vitamin D and calcium alone may be sufficient to correct low bone mineral density encountered in some adults with developmental disabilities( especially those who are found to be deficient in Vitamin D), but others may require a pharmaceutical agent. If a pharmaceutical agent is required, it remains critical that vitamin D be optimized before the drug is started.10 After 3-5 years of continuous bisphosphonate usage, a drug holiday should probably be provided to reduce the possibility of bisphosphonate side effects, such as atypical fracture, osteonecrosis of the jaw, esophagitis and cancer of the esophagus.11
It is difficult to make a generalized statement on exactly how much calcium and vitamin D to give (doses) and what the optimal blood level of vitamin D should be to promote improvement of low BMD. There is general agreement that the administration of 4000-10000 units/day of vitamin D3 is safe. In addition the safe upper limit for calcium administration is a total intake of 2000-3000 mg/day.12 However, regarding individuals who have multiple comorbid conditions that have competing effects on different areas of human body metabolism, more complex therapy must be managed on an individual case-by-case basis and cannot be set into algorithms that might be proper strategies for public health decisions (12). Regarding risk for cardiovascular disease there is no conclusive evidence that serum vitamin D levels between 15-70ng/ml are associated with increased risk, however, there is some evidence for risk of calcium “supplementation” of greater than 500 mg/day.12 Most professional societies suggest an individualized approach with the goal of obtaining a serum 25-hydroxyvitamin D vitamin D level of 30-50ng/ml, and a total calcium intake of 1200 mg/day. However, other conditions (such as some cancers) may benefit from much higher levels of vitamin D.13
Focusing on the problem of low BMD, one study demonstrated a progressive increase of BMD which correlated with a rise of serum 25-hydroxyvitamin from low levels up to as high as 72 ng/ml in adults under 50 years of age. On the other hand, this effect was lost after a level reached 40-50 ng/ml in those over 50 years of age.14 This age-related observation may be explained by less calcium intake, co-morbid conditions, drug effects, and/or reduced physical activity levels in the older group, conditions that develop with aging which may “override” the bone enhancing effects of vitamin D and calcium alone in the elderly group. The argument could be made that the older individuals still might benefit from a trial of a higher dose of vitamin D and/or calcium, that may not correct the problem of low BMD, but it may prevent it from getting worse.
Therefore, it may not be unreasonable to increase 25-hydroxyvitamin D levels (with calcium) to a higher normal range, even in those individuals over 50 years of age, before starting a pharmaceutical. If after a year’s trial at the higher level of 25-hydroxyvitamin D Bone Turnover Markers remain elevated and Bone Mineral Density does not improve, a pharmaceutical could then be started. Since it has been shown that maintaining a serum level of 25-hydroxyvitamin D greater than or equal to 33ng/ml is associated with a 4.5X improvement of effectiveness of administered bisphosphonate, a better outcome from bisphosphonate use after increasing the serum level of 25-hydroxyvitamin D might be expected.10 •
ABOUT THE AUTHOR:
Philip May MD has devoted the past 30 years of his career to improving the quality of health services provided to adults with intellectual and developmental disabilities. In the year 2000 he was recipient of the Arc of New Jersey Health Care Professional of the Year award. He is the co-founder (with Henry Hood DMD) of the American Academy of Developmental Medicine and Dentistry (www.aadmd.org), and also co-founder (with Sunil Wimalawansa MD. PhD) of the International Foundation for Chronic Disabilities (www.chronicdisabilities.org). For the past 10-15 years he has focused on the problems of evaluation and management of osteoporosis and fractures that occur in adults with developmental disabilities. To learn more visit the IFCD YouTube educational site at www.youtube.com/user/philipmay123
1.Zystra, R., et al. Prevalence of Osteoporosis in Community Dwelling Individuals with Intellectual and/or Developmental Disabilities. J. Am. Med. Dir. Assoc. (2008) 9;109-113.
2. Jaffe, J., et.al. Prevalence of Low Bone Mineral Density in Institutionalized Men with Developmental Disabilities. J.Clin. Densitometry(2003)6: 143-147.
3. . Jaffe, J., et.al. Prevalence of Low Bone Mineral Density in Women with Developmental Disabilities. J.Clin. Densitometry (2001)4: 25-29.
4. Glick, N., et.al. Epidemiology of Fractures in People with Severe and Profound Developmental Disabilities. Osteoporosis Int.(2005) 16;389-396.
5. Poole, K. Sclerostin is a Delayed Secreted Product of Osteocytes That Inhibits Bone Formation (2005)FASEB Journal Express Article 10.1096.
6. Heaney, RP, et al, Human Serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003; 77:204-210.
7. Pietras, SM, et al, Vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6 years. Arch Int Med 2009; 169:1806-1808.
8. Holick, MF, et al, Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011; 96: 1911-30.
9. Binkley, N and Lewiecki, EM Vitamin D and Common Sense J Clin Densitometry: Assessment of Skeletal Health 2011; 95-99.
10. Carmel, A.,et.al. The 25(OH)D Level That is Needed to Maintain a Favorable Bisphosphonate Response is > 33 ng/ml. Osteoporosis Int. (Jan.2012)Online Pre-Publication.
11. Ott, Susan. What is the Optimal Duration of Bisphosphonate Therapy? Cleveland Clinic J. of Med(2011) 78; 619-628.
12. Miller, Paul. Vitamin D, Calcium, and Cardiovascular Mortality: A Perspective from a Plenary Lecture Given at the Annual Meeting of the American Association of Clinical Endocrinologists. Endocrine Practice (2011)17; 1-9.
13. Garland, C. et.al Vitamin D Supplement Doses and Serum 25-Hydroxyvitamin D in the Range Associated with Cancer Prevention Anticancer Research (2011)31; 617-622.
Source Exceptional Parent Magazine