Anorexia Nervosa and Its Impact on Bone Health
By Meghan Slattery, MSN, FNP-BC
Why is there a cause for concern?
Low bone mineral density is a pervasive medical complication of anorexia nervosa rising from profound nutritional and hormonal deficiencies. Bone loss can be severe even early in the course of illness. More than 50% of adolescent females with anorexia nervosa show significant bone loss less than one year from diagnosis. Adult females are also impacted; in one study, 92% of adult females had low bone mineral density (osteopenia) at one or more sites in the body and close to 38% had osteoporosis in at least one area . Of concern is the increased risk for fractures resulting from this low bone mineral density. In older adults, each standard deviation reduction in bone mineral density (when measured by a bone density scan) doubles a person’s fracture risk . Among girls 12 to 22 years old, those with anorexia nervosa have a 1.6 times greater risk of fracture than those without anorexia nervosa . Similarly, low weight adult females have an elevated overall risk of fracture, and specifically in the spine and forearm. 
Role of Genetics, Calcium, Vitamin D and Hormones
An individual’s bone density is determined to a great extent (60-70%) by family history and genetic make-up . However, diet also plays a major role, and nutritional deficiencies can directly impact bone health. In addition to other functions, bones serve as a warehouse, storing about 99% of the calcium in the body, which in turn is critical for bone mineralization and thus contributes to bone strength. In addition to strengthening bones, calcium is essential for the normal functioning of muscles and nerves. If a person’s diet is calcium deficient, bones will be robbed of calcium to maintain normal blood levels for vital functions. This leads to bone demineralization and reduced bone strength. Vitamin D is essential to absorb dietary calcium, and vitamin D deficiency, even in the presence of adequate calcium intake, can lead to lower bone density.
Our bones, strong and invulnerable as they seem, are very sensitive to alterations in hormone levels, particularly estrogen. The body responds to a starved state by conserving resources when possible, e.g. limiting reproduction by minimizing production of estrogen and of certain hormones that regulate ovarian production of estrogen. This disruption in normal estrogen levels may manifest as absent or irregular menstrual cycles, and contribute significantly to bone loss. Bone density is impacted by both bone formation and bone loss. While estrogen deficiency increases bone loss, anorexia nervosa is also associated with reduced bone formation. Bone formation (buildup) is largely stimulated by another nutritionally regulated hormone, insulin-like growth factor 1 (IGF-1). Like estrogen, in a setting of nutritional restriction, IGF-1 levels are reduced, decreasing bone formation and increasing the likelihood of low bone density . In addition, due to demands placed on the body, individuals with anorexia nervosa often produce excessive amounts of the stress hormone cortisol, which further precipitates bone loss while also reducing bone formation.
Impact on Peak Bone Mass
In healthy teenagers, due to the pubertal increase in hormones including estrogen and IGF-1, bone mass increases rapidly during the teenage years. Bones reach 90% of their peak mass by approximately 18-20 years of age. Shortly thereafter, peak bone mass is attained, which is a key determinant of future bone health . Adolescents with anorexia nervosa have significantly lower bone accrual rates compared to adolescents without an eating disorder  and consequently may not build as much bone during the teenage years as their genetics and family history would predict. Because peak bone mass is an important determinant of future bone density and fracture risk, this reduction becomes a major risk factor for poor bone health. Strikingly, bone density is lower in women who develop anorexia nervosa during the adolescent years compared to women with disease onset in adulthood, despite a similar duration of illness . Adolescence accordingly is the critical window of time during which intervention is likely to be most efficacious in improving future bone health. Without intervention, inadequate bone accrual may result in sufficient reduction in peak bone mass that deficits become permanent.
Can low bone density be “fixed”?
What does this mean for adolescents with anorexia nervosa, or for those who are well past their adolescent years? Although anorexia nervosa affects bone density rapidly and severely, strategies do exist to address bone loss or poor bone accrual, especially if recognized early. Overwhelmingly, the best approach to increase bone accrual and improve bone density is to regain and maintain a healthy weight. This weight restoration prevents further bone loss by contributing to both the normalization of hormone levels and the return of regular menstrual cycles. There is evidence that bone density improves as weight increases, even before return of spontaneous menses.
Osteoporosis is referred to as the “Silent Disease”, because whether bone is lost gradually or rapidly, there are minimal symptoms. The lack of physical symptoms means that recognizing the red flags for low bone density early is essential to reverse its course. Having a discussion with a health care provider who can order a dual energy x-ray absorptiometry (DEXA) scan is an excellent starting point. A DEXA scan is a safe and painless test that is useful in detecting bone loss before a fracture occurs. In adults, it can also predict the chance of a future fracture. These scans may be covered by insurance and can be ordered and interpreted by primary care providers.
While working towards weight gain and menstrual recovery, and even before a DEXA scan is performed, nutrition changes can be made to optimize intake calcium and Vitamin D. A well-balanced diet, rich in sources of calcium and vitamin D (such as dairy, green leafy vegetables, certain fishes like salmon or tuna, egg yolks) is helpful for bone health in conjunction with other treatments. While dietary sources allow for much better absorption, inadequate calcium and Vitamin D intake can also be addressed with supplements. Of importance, optimization of calcium and Vitamin D alone will not effectively normalize bone density. Though not discussed here, smoking and excessive alcohol lead to increased bone loss and decreased bone buildup respectively. Quitting either can help prevent a continued worsening of bone density.
Is there a role for estrogen replacement?
Since estrogen helps prevent bone loss, a common practice has been to prescribe oral contraceptive pills (OCP) to girls and women with anorexia nervosa with the goal of menstrual cycle restoration. Yet, despite the frequency of such prescribing practices, there is actually limited to no medical benefit from use of estrogen-progesterone combination pills in those with low-weight eating disorders when given solely for improving bone health. In fact, having an OCP induced menstrual cycle may give patients or their families a false sense of security that the individual is ‘protected’ from the deleterious effects of low estrogen levels associated with loss of periods, and that weight restoration and recovery can therefore “wait”. It also takes away a helpful marker of how recovery is progressing i.e. the return of menstrual function. Despite the key role of estrogen in preventing bone loss, research has shown that the estrogen in OCPs typically does not improve bone density in women with low-weight eating disorders lacking estrogen. This is likely because estrogen taken orally is first processed in the liver, the site of IGF-1 production, and causes a subtle, but significant enough reduction in IGF-1 levels to prevent an improvement in bone density 
More recent and promising research has shown that estrogen provided in its natural form via a transdermal patch to teenage girls with anorexia nervosa causes an increase in bone density (similar to that seen in healthy girls), although complete normalization does not occur. In two current clinical trials at Massachusetts General Hospital we are assessing whether providing IGF-1 in replacement doses is effective in further increasing and potentially normalizing bone density in adolescent and adult women with anorexia nervosa. Other treatments are also actively being researched.
A class of medication called bisphosphonates, which are FDA approved to treat osteoporosis in postmenopausal females, have been shown to increase spine and hip bone density in adult females with anorexia nervosa . Despite these promising results from one study, the same effects have not been seen in an adolescent population. For this reason and their long half-life (meaning they may be present in the bloodstream for years post discontinuation), their use is not recommended at this time in a younger population.
Does Exercise help or hurt?
Exercise in children and adults of a healthy weight has beneficial effects on bone. In particular, weight-bearing exercise (walking, weight training, tennis) can be helpful in post menopausal females with osteoporosis. However, in people who are underweight, have anorexia nervosa, or irregular menstrual cycles due to undernutrition, exercise may pose an additional risk. One study found bone density in the spine and whole body in females with anorexia nervosa to be lower among those engaged in moderate levels of exercise (such as walking or pacing) compared to women who were not exercising. However, after recovery, women who engaged in weight bearing exercise had higher bone mineral density in the hip and whole body than those who were not exercising; showing that the bone building benefits of exercise exist, but may begin only AFTER recovery.  Importantly, advice must be sought from an eating disorder specialist prior to engaging in exercise during recovery from anorexia nervosa. Without a full medical evaluation and clearance, exercise, especially if prolonged or intense, may worsen not only bone health, but electrolyte values as well as heart and brain function.
The Bottom Line
Despite being considered a disease only of the elderly, low bone density is a debilitating complication in patients of any age with low weight eating disorders. The causes of low bone density are multifactorial and it follows then that possible treatments need to address these causes. The first and most important step is to recognize and minimize risk factors for bone loss. The earlier low bone density is recognized, the higher the likelihood it can be addressed successfully.
About the author:
Meghan Slattery is a board-certified Family Nurse Practitioner in the Neuroendocrine Unit of Massachusetts General Hospital, specializing in eating disorders in adolescents. She received both her Bachelor and Masters in Nursing from the University of Pennsylvania. She worked at NYU Langone Medical Center and the University of Pennsylvania prior to joining the Neuroendocrine Unit.
- Bachrach, L.K., et al., Decreased bone density in adolescent girls with anorexia nervosa. Pediatrics, 1990. 86(3): p. 440-7.
- Grinspoon, S., et al., Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann Intern Med, 2000. 133(10): p. 790-4.
- Cummings, S.R., et al., Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet, 1993. 341(8837): p. 72-5.
- Faje, A.T., et al., Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa. Int J Eat Disord, 2014. 47(5): p. 458-66.
- Bachmann, K.N., et al., Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa. J Clin Endocrinol Metab, 2017. 102(1): p. 57-68.
- Bachrach, L.K., Acquisition of optimal bone mass in childhood and adolescence. Trends Endocrinol Metab, 2001. 12(1): p. 22-8.
- Locatelli, V. and V.E. Bianchi, Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis. Int J Endocrinol, 2014. 2014: p. 235060.
- Misra, M., et al., Weight gain and restoration of menses as predictors of bone mineral density change in adolescent girls with anorexia nervosa-1. J Clin Endocrinol Metab, 2008. 93(4): p. 1231-7.
- Biller, B.M., et al., Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa. J Clin Endocrinol Metab, 1989. 68(3): p. 548-54.
- Misra, M., et al., Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. J Bone Miner Res, 2011. 26(10): p. 2430-8.
- Miller, K.K., et al., Effects of risedronate and low-dose transdermal testosterone on bone mineral density in women with anorexia nervosa: a randomized, placebo-controlled study. J Clin Endocrinol Metab, 2011. 96(7): p. 2081-8.
- Waugh, EJ, Effects of exercise on bone mass in young women with anorexia nervosa. Med Sci Sports Exerc, 2010. 43: p. 755-763.