Fight for a Future

OSTEOPOROSIS

January, 2005

(IN PRESS: Neuromuscular Disorders 15 (2005) 80–85): Bone health in Duchenne muscular dystrophy: a workshop report from the meeting in Cincinnati, Ohio, July 8, 2004

W.D. Biggar, L.K. Bachrach, R.C. Henderson, H. Kalkwarf, H. Plotkin, B.L. Wong - Canada and USA

Summary and next steps

From the workshop discussions, there is general agreement that:

DMD is associated with reduced mobility.
Boys with DMD have an increased risk of fractures, particularly long bones.
DMD patients have reduced bone mineral density.
Corticosteroids may be associated with a further reduction in bone mineral density.

The bone mineral density Z- cannot be used to predict fracture risk, and it should not be used alone to make treatment decisions.

Corticosteroids may increase the risk of a vertebral compression fracture, many of which are asymptomatic.
Vitamin D and calcium contribute to bone health but have not been proven to reduce the risk of low-impact fractures.
The best sources of calcium and vitamin D are a balanced diet and sunshine.
It is recommended that boys with DMD have a serum vitamin D determined annually; supplementation is appropriate if the concentration is <20 ng/ml.

But, we need to determine:

How best to assess and monitor bone health.
The natural history of bone health in DMD.
Risk factors that predict the likelihood of a low-impact fracture.
The contribution of Vitamin D and calcium to bone health in DMD.
Potential interventions involving weight-bearing activities to maintain bone strength.
What strategies are effective in preventing and treating reduced bone mineral density.
How to develop multicenter, collaborative study groups in order to.
Collect standardized, clinical and laboratory data on boys with DMD, and
to collect clinical trials to improve bone health and quality of life for boys with DMD.

2003 september 15

Use of Alendronate to treat osteoporosis in boys with muscular dystrophy: a report of 3 cases. NEW

Susan D. Apkon, MD (Children's Hospital and University of Colorado Health Sciences Center, Denver, CO), e-mail: apkon.susan@tchden.org

Archives of Physical Medicine and Rehabilitation - 2003 Academy annual assembly abstracts Setting: Tertiary care pediatric hospital. Patients: 2 boys with Duchenne’s muscular dystrophy (DMD), ages 11 and 12 years, and 1 boy with Becker’s muscular dystrophy (BMD), age 11 years. All boys are ambulatory for a portion of the day. Case Descriptions: Baseline bone mineral density of the lumbar spine and femoral neck were assessed using dual-energy x-ray absorptiometry (DXA). Results revealed significant osteoporosis at the femoral neck, with a mean z score (SD using ageand sex-matched peers) of –3.73 (range, –3.16 to –4.42). Results at lumbar spine revealed mean z score of –1.14 (range, –1.6 to 0.82). Because all subjects were having frequent falls, parents and physicians felt aggressive treatment was necessary to prevent fractures. Oral alendronate was initiated at 45mg weekly for 6 months. Assessment/Results: All 3 subjects tolerated the medication without side effects. There were no gastrointestinal complaints. Follow-up DXAs performed after 6 months of treatment revealed improvements at the femoral neck in all 3 subjects, with a mean improvement in z score of 0.94 (range, 0.3–1.33) representing an improvement of almost 1 SD. There was improvement at the lumbar spine, with a mean change of 0.28 (range, –0.45 to 1.11). Discussion: Osteoporosis is problematic in boys with DMD and becomes more severe as the disease progresses. The high incidence of fractures in this group of boys is likely due to osteoporosis. This is the first known report on the use of alendronate in children with DMD or BMD in the treatment of osteoporosis. Conclusion: In this small case series, weekly oral alendronate over 6 months was effective in improving bone mineral density in boys with DMD and BMD. A prospective, randomized, double-blinded study is underway.

2003 Jul 29

Bone mineral density and bone metabolism in Duchenne muscular dystrophy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12897980&dopt=Abstract

DMD and Osteoporosis by Ana Lucia Langer, MD
Posted 12.05.2003

Until recently, the doctors believed that the bone loss that occurs in DMD would be consequent of immobilization or the use of medications. Currently, osteoporosis has been observed, mainly in the lumbar column and femoral head, in the boys who still are walking and without the use of drugs that could lead to the reduction of bone mass, such as steroids. Scoliosis, which also occurs in a great percentage in DMD, is a factor that speeds up the loss of bone mass.

Steroids and Osteoporosis
The deleterious effect on the bone of steroids are well known. They act in different spheres:

a) In the cellular level they act directly inhibiting the function of the osteoblasts (cells for reconstruction of the bone)

b) the steroids stimulate the activity and increase the number of osteoclasts (cells for absorption of the bone)

c) also leads to a malabsorption of intestinal calcium, dependent dose, and it occurs in first the 2 weeks of therapy; The reduction of the intestinal absorption of calcium leads to the stimulation of the parathyroid hormone (secondary hyperparathyroidism) aiming at the maintenance of the blood calcium level. We have, as a consequence, an increase of the urinary excretion of calcium and, therefore, reduction of available calcium.

d) The steroids therapy brings negative effect for the secretion of sexual hormones. As example we have the retardation of puberty, the lesser production of testosterone in patients of the masculine sex (about 50% minor). The reduction of sexual hormones also contributes for the reduction of the mineral content of the bone.

During the first year of steroid use, loss of 5% of bone mass occurs. Later, this loss falls for 0.3 to 3% in the subsequent years. The loss is more intense in the first 6 months and is dose and time dependent. For this, all patients that receive steroids treatment need a planning for prophylaxis of osteoporosis in the initial phases of therapy.

Diagnosis: we study the bone density through the DEXA, dual energy X-ray absortiometry. Ideal It is an examination because it's not invasive and will consider the diagnosis of loss of bone mass and you predict the risk of fractures. X - Ray is not an adequate procedure that would demonstrate bone rarefaction when the bone loss will be around 50%. When the bone density demonstrated osteoporosis there is increase of fractures risk, also of vertebral column, indicating the pressing necessity of an aggressive treatment.

Treatment: 1) Diet must be enriched with calcium and vitamin D. Vitamin D is a necessity; you improve the intestinal calcium absorption and you prevent the excess of excretion through urine. Normally it is ingested pre-vitamin and needs solar light or, you change your activation form.

The recommendation of the daily vitamin D necessities is the following:

young children and adults 200 IU
adults over 51 years - 400 IU
adults over 71 years - 600 IU

These doses need to be reviewed by individuals that do not take sun, completely keeps their bodies covered, or because they use steroids.

The recommended dose of calcium is:

children - 4 through 8 years: 800 mg
children - 8 through 19 years: 1300 mg
adults- 1000 1200 mg

In DMD patients has a great concern with the caloric restriction. A rich diet in calcium associated with low caloric diet can be a difficult challenge of being looser. In these cases, the use of supplements is a factor of important prophylaxis for osteoporosis. The relation calcium and phosphorus is primordial. For an excellent absorption it is necessary that it is of 2:1. The excessive ingestion of phosphorus has negative impact in the bone mineral accumulation as it increase urinary excretion of calcium. Red meats in excess must be prevented, soft drinks as coke or similar, processed foods with additives with phosphorus or phosphates too. Salt and caffeine (again coke, coffee, tea) are common causes of loss of calcium in urine and must be prevented.

The vegetables, the nuts, the grains, the soy, the green grain of peak, vegetables (swiss chard, watercress, turnip, beetroot leaves, radish, parsley, brocolis) and dairy products are rich calcium sources.

Exercises: One of the best exercises for osteoporosis is walking. The exercises must be diversified, with some levels of resistance and developed efforts of an aerobic form. They must be preceded by warming up and be followed by stretching and , ideally, should be supervised by qualified professionals; in patients with neuromuscular diseases this type of orientation with frequency is not possible of being observed. In these cases the orientation is the following:

- For the patients who cannot walk , but they can stand, that tries to make it some times to the day. This bone stress has a positive effect. The equipments and wheelchair that help the patient in stand can be coadjuvant in this treatment.

- Swimming exercises, althrough not ideal as they do not promote bone stress, are better than no exercise at all.

- Passive exercise aimed out by specialized professionals can be of help for those without any possibilities of movement.

Drugs - Biphosphonates. Its main representatives are the etidronate, alendronate and risedronate. They are powerful inhibitors of bone reabsortion. It stimulates the function of the osteoblasts (cells for reconstruction of the bone). In vitro it stimulates the osteoblasts proliferation. Other actions: it increases the intestinal calcium absorption, stimulates the formation of the colagen of the cartilage, inhibits the lactic acid and the synthesis of prostaglandins. These are the most important drugs to use in osteoporosis, as much for treatment as for prevention. They are also the drugs for use in the fight of the side effects of steroids in the bone. The use of the drug can reduce the fractures of the vertebral column in 70% after 1 year of use.