Trip Answers

Question answered:05/01/09

UPDATE: JANUARY 2009

The NeLM have recently published a Q&A on this topic (http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Medicines-Q--A/Can-antiepileptics-anticonvulsants-increase-the-risk-of-osteoporosis/).  This reports:

 

"• Phenytoin, phenobarbitone and carbamazepine have been associated with reduced BMD and increased fracture rates which are characteristic of osteoporosis. • There have been no adequate studies and only a few anecdotal reports of reduced BMD with the newer AEDs such as valproate and lamotrigine and consequently there is insufficient data to establish a definitive conclusion. Further studies are necessary with these agents. • The incidence and type of bone disease with AEDs has not been adequately assessed to date and the exact mechanism of AED associated bone disease has not been fully elucidated. • Polytherapy with multiple AEDs is associated with a higher risk of bone abnormalities, however no single combination of AEDs has emerged as most likely to cause this. • Peak BMD is established during childhood and adolescence. One study has reported that treatment with valproate and/or lamotrigine for greater than 2 years is associated with short stature, low bone mass and reduced bone formation. • The correlation between duration of therapy and bone disease is unclear. There have been reports of epileptic patients with a history of childhood and adolescent anti-epileptic use developing osteopenia by age 40. One study concluded that a reduction in BMD associated with valproate increased with duration of therapy. Changes in bone density and fracture risk may occur at a younger age in AED users than in the general population. • No definitive guidelines for the evaluation, prevention and treatment of AED induced bone disease have been determined. It has been suggested that all patients taking barbiturates, phenytoin and possibly carbamazepine should be considered for calcium and vitamin D supplementation."

 

Initial Answer

 

We found a number of articles that discuss the use of anticonvulsants and osteoporosis.  Due to the number we will report on only a small number.  If further information is required then get back in touch via ‘Contact Us’ (http://www.clinicalanswers.nhs.uk/index.cfm?action=contact)

 

“In perimenopausal women, more than 50 percent is associated with secondary causes, and the most common causes are hypoestrogenemia, glucocorticoids, thyroid hormone excess, and anticonvulsant therapy.” [1]

 

“Vitamin D is not widely available in natural food sources. It is primarily found in fish oils (including cod liver oil), some vegetables, and fortified milk, cereals, and breads. Supplements of 400 IU daily should be prescribed for younger adults. Supplements of 800 IU daily should be prescribed for elderly patients (in whom vitamin D absorption may be reduced), malnourished patients, patients with intestinal malabsorption, and patients receiving long-term anticonvulsant or glucocorticoid therapy.” [2]

 

“Causes: … Anticonvulsants (eg, phenytoin, barbiturates, carbamazepine) - Due to treatment-induced vitamin D deficiency and resultant decreased intestinal calcium absorption and secondary hyperparathyroidism” [3]

 

Finally, the UK’s National Osteoporosis Society has a patient information sheet on the osteoporosis and anti epileptic drugs [4].  The most pertinent passage relating to the question is:

 

“How do anticonvulsant drugs affect bones and increase the risk of osteoporosis and broken bones?

 

Anticonvulsant drugs are used mainly for the condition called epilepsy which causes seizures, sometimes called ”fits‘. Anticonvulsant drugs are thought to affect bone density (the quantity of bone that when measured helps to indicate bone strength) by affecting the way vitamin D is broken down and used by the body. Vitamin D helps the body absorb calcium which is a vital nutrient for bones. Most people obtain the majority of their vitamin D from exposure to sunlight. Severe vitamin D deficiency can also cause osteomalacia (softening of the bones) in adults, which is also called rickets in children.

 

The risk factors associated with anticonvulsant induced osteoporosis, include high doses of drugs, multiple drug regimes (where more than one drug is used), long term use and staying indoors with little normal exposure to sunlight resulting in vitamin D deficiency.”

 

References

1) NIH Consensus Statement. Osteoporosis Prevention, Diagnosis, and Therapy. 2000 (http://consensus.nih.gov/2000/2000Osteoporosis111PDF.pdf)
2) American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. (http://www.guideline.gov/summary/summary.aspx?doc_id=4157&nbr=3185&ss=6&xl=999)
3) eMedicine. Osteoporosis. 2005 (http://www.emedicine.com/med/topic1693.htm)
4) NOS. Anti epileptic drugs and osteoporosis. (http://www.nos.org.uk/documents/AntiEpilepticDrugsandOsteoporosis.pdf)
 

---

DISCLAIMER: TRIPanswers is a collection of clinical questions and answers.  Each provider will have their own methodology in answering questions and these are likely not to be as rigorous as systematic review.  If you have any doubt as to the implications of this contact the Q&A Service Provider for further information. This document is presented for information purposes only. This document cannot and should not be used as a basis of diagnosis or choice of treatment, and is in no way intended to replace professional medical care or attention by a qualified practitioner. TRIPanswers and TRIP Database Ltd are not responsible or liable for, directly or indirectly, ANY form of damage whatsoever resulting from the use/misuse of information contained in or implied by this document.  Also, ensure you have read the terms and conditions for using the site.