Clinical Briefs

By Louis Kuritzky, MD

Oral Vitamin D3 Supplementation on Fractures and Mortality

Despite recent enhanced clinician and public awareness, prevention and treatment goals for osteoporosis (OSPS) remain inadequately fulfilled. A variety of lifestyle and pharmacologic tools have been applied to OSPS management, including Vitamin D (VitD) supplementation, with some, albeit inconclusive, success.

This trial was a pilot study using VitD (cholecalciferol) supplementation in a British senior citizen population (age range, 65-85) solicited by mail (n = 2686) to participate in a placebo-controlled trial lasting 5 years. Unusual in this trial was the dosing methodology, which administered a single 100,000 IU VitD capsule once every 4 months for 5 years—not once daily, but once (total capsules administered in 5 years = 15). Participants were instructed to take the capsule they received in the mail immediately upon receipt, and respond by mail on a form indicating that they had indeed taken the medication.

Compared to placebo, the treatment group had a 22% lower rate for first fracture (any site) and a 33% lower hip, wrist, forearm, or vertebrae fracture rate. The parathyroid hormone concentrations did not differ significantly between active VitD and placebo, despite a 40% higher VitD level in the former.

Ultimately, the 100,000 IU dose of VitD is approximately equivalent to 800 IU per day, which has been used in other trials. However, the convenience, lack of toxicity, and monetary savings (in the United Kingdom, 3 capsules of 100,000 IU vitD costs less than 1 pound) provide intriguing stimuli for a larger trial.

Trivedi DP, et al. BMJ. 2003;326: 469-472.

Oral Opioid Therapy for Chronic Peripheral and Central Neuropathic Pain

Neuropathic pain (NPP) is often described as "opioid resistant," based upon some limited human and animal studies. On the other hand, parenteral opioid analgesia has produced success in NPP. Although data on postherpetic neuralgia indicate a degree of efficacy with opioid analgesia, other NPP syndromes are not well studied in prospective, blinded studies.

Because of the ethical boundary of administering placebo to patients suffering chronic pain, a study was performed comparing 2 different dosing levels of levorphanol, a potent mu-opioid agonist, for patients (n = 100) suffering chronic NPP, in a double-blind fashion. Patients were administered either 0.15 mg or 0.75 mg capsules, and allowed to titrate up to as many as 7 capsules 3 times daily (levorphanol has a 6-8 hour duration of analgesia). The primary outcome of the study was degree of pain reduction; secondary outcome was time to pain relief. The study period was 8 weeks duration.

As perhaps might be intuitive, high-strength levorphanol reduced pain to a significantly greater degree than in the lower-strength group, despite the option available to patients of up-titrating their medication dose. Encouragingly, both groups did report levorphanol efficacy (pain reductions, 21% and 36%). Contrary to popular wisdom, tolerance to opioid analgesia was not evidenced. Additionally, the magnitude of pain reduction in the high-strength group was similar to that achieved with other more traditionally used NPP tools like tricyclic antidepressants and gabapentin.

Clinicians who have excluded opioid analgesia as an effective tool in NPP may need to consider these data in their decision process.

Rowbotham M, et al. N Engl J Med. 2003;348:1223-1232.

Tacrolimus Ointment vs. Topical Corticosteroids in Adults with Moderate-to-Severe Atopic Dermatitis

For several decades the mainstay of management of atopic dermatitis (AD) has been corticosteroids (CSD), usually administered topically. When AD is mild-moderate, low, and mid-potency, CSD often suffices, but more severe disease may require high-potency agents, or even systemic therapy. Since CSD can produce both local effects like skin atrophy and systemic effects such as hypothalamic-pituitary suppression, chronic administration requires a degree of caution. Recently, a class of topical immunomodulator agents (IMA), exemplified by tacrolimus (Protopic) and pimecrolimus (Elidel), has been offered for clinical use as an alternative to CSD and appears to be equally efficacious. There are no serious side effects of IMA, and they have been demonstrated to be both safe and effective in children as young as 2 years, with minimal side effects.

For patients with moderate-to-severe AD, the cost of treatment was similar for either high-potency CSD and IMA for a 4-week treatment regimen. For short-term treatment (2 weeks), IMA is more cost effective than CSD because there is less requirement for secondary interventions. If lower potency and less costly CSD are used efficaciously, the cost efficacy of IMA becomes less favorable. The combination of safety, efficacy, and cost has important therapeutic implications for the role of IMA in AD.

Ellis C, et al. J Am Acad Dermatol. 2003;48:553-563.

Dr. Kuritzky is Clinical Assistant Professor, University of Florida, Gainesville.