Clinical Briefs-By Louis Kuritzky, MD

Parathyroid Hormone (1-34) in Postmenopausal Women with Osteoporosis

Though numerous agents for prevention and treatment of osteoporosis (OSPS) are available, none is ideal for all women, and each has a distinct limitation. The dominant function of most agents is to inhibit bone resorption, thereby reducing bone loss, but doing little to increase, or stimulate, new bone formation. Hence, the idea of using a therapy that stimulates bone formation is appealing.

Neer and associates point out that parathyroid hormone (PTH) has various effects upon bone, depending upon administration method. To test the hypothesis generated by successful animal studies, Neer et al studied PTH (vs. placebo) in postmenopausal women (n = 1637) with prior vertebral fractures. PTH was self-administered by injection daily for 24 months. All subjects also received vitamin D and calcium supplementation.

There were statistically fewer new nonvertebral fractures in the PTH treatment group than placebo (RR = 0.47); similarly, bone mineral density increased 9-13% more than placebo recipients. The medication was well tolerated, with no serious side effects. PTH has been shown to be effective in preventing fractures and stimulating bone formation.

Neer RM, et al. N Engl J Med. 2001; 344:1434-1441.

Biochemical Markers of Liver Fibrosis in Patients with Hepatitis C Virus Infection

It is common practice to perform liver biopsy for definition and prognostication of hepatitis C (HEPC). This process is not without consequence: although mortality is rare (0.03%), other serious complications are significantly more common (0.3%), not to mention the pain at the time of biopsy, and in 30%, postbiopsy pain. Imbert-Bismut and colleagues sought to evaluate the predictive value of basic serum biochemical markers for the diagnosis of liver fibrosis, (early as well as advanced). If indeed such markers had valuable predictive capacity, some liver biopsies might be avoided.

Imbert-Bismut et al studied 11 different serum markers, including traditional transaminases, alpha-2 macroglobulin, haptoglobin, gammaglobulin, apolipoprotein A-1, gammaglutamyltranspeptidase, and total bilirubin. The study group included 205 HEPC patients who had undergone liver biopsy. Serum markers were assayed in years 1 and 2.

Twelve percent of patients had sufficiently low scores using multiple serum markers that liver biopsy could have been avoided with 100% certainty that no significant fibrosis was present. Imbert-Bismut et al suggest that use of serum markers may substantially reduce unnecessary liver biopsy in patients with HEPC.

Imbert-Bismut F, et al. Lancet. 2001; 357:1069-1075.

Management of Chronic Tension Type Headache

Chronic tension type headache (CTH) is defined by the International Headache Society criteria as occurring 15 or more days/month for at least 6 months. Since this disorder is not infrequent (1.5% of men, 3% of women) and results in decrements in quality of life, as well as decreased work performance, choosing the most efficacious management is of great clinical relevance.

The current study was a randomized placebo-controlled trial (n = 203) comparing tricyclics (TCA) with stress management, or the combination. TCA therapy used amitriptyline or nortriptyline, titrated from a low starting dose, to maximize tolerability, up to 100 mg/d of amitriptyline or 75 mg/d nortriptyline.

Stress management techniques (SMT) included deep muscle relaxation, instruction in cognitive coping skills, and guidance in stress management. Treatments (or placebo) were administered for 6 months.

Each active treatment arm was significantly more effective than placebo. TCA therapy had the greatest number of individuals with improved headache score (38%), followed by stress management (35%). The combination of treatments was most effective, producing a favorable response in 64% of subjects. Holroyd and colleagues conclude that a combined approach to CTH results in the most favorable outcome.

Holroyd KA, et al. JAMA. 2001;285: 2208-2215.