Treatment of X-linked hypophosphatemia (XLH) into Adulthood May Prevent Dental Disease

Commentary by Thomas O. Carpenter, MD and Courtney Kloberdanz, DDS

Dental X-RayExposure during adulthood to the standard therapeutic regimen for X-linked hypophosphatemia (XLH) of calcitriol and phosphate neither prevents nor promotes the development of enthesopathy. On the other hand, greater exposure to this therapy in adulthood was associated with fewer dental abscesses in this population, according to an observational cross-sectional study published in the October Journal of Clinical Endocrinology and Metabolism.

“Historically, adult treatment has been somewhat controversial, with less than half of the patients with this disease being treated after their childhood growth is finished,” explained senior author Thomas O. Carpenter, MD, Professor of Pediatrics (Endocrinology) and of Orthopaedics and Director of the Yale Center for X-Linked Hypophosphatemia at Yale University in New Haven, Connecticut

“Because the treatment for XLH enhances mineralization of the bone, there has always been a concern that treatment might accelerate the development of mineralization of the tendons and ligamentous insertions sites (enthesopathy) in adulthood,” Dr. Carpenter said. “This study provides data regarding outcomes of XLH patients’ exposure to treatment in their adult years. We found no relationship of the treatment exposure to the extent of enthesopathy,” Dr. Carpenter said. In addition, treatment had a discernible effect of helping patients’ teeth in adulthood, Dr. Carpenter said.  

Treatment Had No Effect on Enthesopathy
The study involved 52 patients (ages ≥18 years) with XLH. The main outcome measures were the number of enthesopathy sites assessed radiographically and the severity of dental disease, categorized as >5 or ≤5 dental abscesses identified historically. The number of enthesopathy sites was not associated with the proportion of adulthood or total life during which patients received treatment with calcitriol and phosphate.

Treatment Benefited Patients’ Teeth
In contrast, both the proportion of adulthood and total life under treatment were significant predictors of dental disease severity (multivariate-adjusted global P=0.0080 and P=0.0010, respectively). Patients who did not receive treatment in adulthood had a 25-fold greater likelihood for having severe dental disease (>5 reported dental abscesses) compared with patients treated their entire adult life. Longer duration of treatment in adulthood was associated with decreasing risk for severe dental disease (multivariate-adjusted P for trend = 0.015)

“These are two of the most significant problems that adults with XLH face. These findings make the case that treatment should be a consideration after the end of growth,” Dr. Carpenter said.

“Treatment of XLH in adulthood has to be decided on a case-by-case basis,” Dr. Carpenter added. Treatment may be best for patients who have severe enough disease that treatment will make a noticeable clinical difference and who will be compliant with the treatment regimen and monitoring protocol, he said. “The treatment can have significant side effects, requires administration of medication several times a day, and monitoring by blood and urine testing. Compliance with monitoring is essential if you treat such patients,” he concluded.

“The findings suggest that dentists should be aware of their patient’s medical history, specifically regarding XLH, and with the support of the patient’s physician, consider lifelong treatment with calcitriol and phosphate,” commented Courtney Kloberdanz, DDS, who specializes in general and restorative dentistry and practices in Chicago, IL.

“It is known that demineralization and remineralization of teeth is continuously occurring,” Dr. Kloberdanz said. “Prevention of caries occurs when the balance is more frequently in favor of remineralization. Such an environment for remineralization includes a higher pH (7.5-8.5) and the presence of calcium and phosphate. In an environment that consistently favors demineralization, dental caries will eventually occur. The presence of untreated, active caries, then may lead to tooth necrosis via bacterial invasion and subsequent abscess.

“This study suggests that supplementation of calcitriol and phosphate, reduces occurrence of dental abscess, by way of reducing dental caries through prevention of demineralization of teeth,” Dr. Kloberdanz said. “However, it is important to remember that not all dental abscess’s are caused by bacterial invasion through the enamel and dentin (AKA caries). Some dental abscesses are caused by bacterial invasion through the sulcus of the tooth, such as in advanced periodontal disease. In future studies it is important to classify the type of dental abscess: is it primarily periodontally caused, or endodontically caused? Making this differentiation will help to determine, by how much, and if at all, treating XLH with calcitriol and phosphate reduces dental disease,” Dr. Kloberdanz said.

 

November 10, 2015

 

 

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