Takaisin

Bisfosfanaattien käyttö laihuushäiriöiden luukadon hoidossa

Näytönastekatsaukset
Laure Morin-Papunen
18.9.2014

Näytön aste: A

Bisfosfonaattihoito parantaa luuntiheyttä laihuushäiriöpotilailla, mutta hoidon merkityksestä murtumien ehkäisyssä ja hoidon turvallisuudesta ei ole riittävästi tietoa.

The objectives of this randomized double-blinded trial «Golden NH, Iglesias EA, Jacobson MS ym. Alendronat...»1 was to compare alendronate (10 mg daily) with placebo. The patients were 32 adolescents with anorexia nervosa (mean age, 16.9 ± 1.9 yr). All subjects received 1 200 mg elemental calcium and 400 IU vitamin D daily and received the same multidisciplinary treatment for their eating disorder. Bone mineral densities (BMDs) of the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry at baseline and after 1 yr of treatment. Twenty-nine subjects completed the study. From baseline to follow-up, BMD increased significantly at the femoral neck (P = 0.02) and lumbar spine (P = 0.02) in those receiving alendronate, but did not increase in those assigned placebo (P = 0.22, femoral neck; P = 0.18, lumbar spine). However, at follow-up, body weight was the most important determinant of BMD. BMD was significantly higher in subjects who were weight-restored compared with those who remained at low weight (P = 0.002, femoral neck; P = 0.04, lumbar spine). After controlling for body weight, treatment group assignment still had an independent effect at the femoral neck.

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

This randomized placebo-controlled study «Nakahara T, Nagai N, Tanaka M ym. The effects of b...»2 on the effects of etidronate and calcium (600 mg/d) and vitamin D (10 µg/d) on bone loss was conducted in 41 outpatients with the restricting type of anorexia nervosa. Measure of the tibial speed of sound (SOS) before and after 3 months of treatment. The bone mineral density (BMD) of the tibial SOS change in both the etidronate group (n=14) and the calcium and vitamin D group (n = 15) was significantly greater (p < 0.001) than in the control placebo group (n = 12). Urine-N-telopeptide cross-links of type I collagen (NTx) before and after treatment decreased significantly (p < 0.01) in the etidronate group.

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: hyvä

This 12-month, randomized, placebo-controlled study «Miller KK, Meenaghan E, Lawson EA ym. Effects of r...»3 investigated the effect of risedronate alone or its combination with low-dose transdermal testosterone on bone density in women with AN. BMD at the spine (primary endpoint), hip, and radius and body composition were measured by dual-energy x-ray absorptiometry. After baseline evaluation, 77 women with AN were randomized to receive 1) risedronate 35 mg weekly plus a placebo patch (n = 20), 2) testosterone 150 μg daily patch plus a weekly placebo pill (n = 19), 3) risedronate 35 mg weekly plus testosterone 150 μg daily (n = 20), or 4) double placebo (n = 18) for 12 months. Follow-up visits were performed at 1, 3, 6, 9, and 12 months after the baseline evaluation. BMD and body composition were assessed at 6, 9, and 12 months after randomization. Markers of bone metabolism, total testosterone, free testosterone, and ALT were measured, and hirsutism (by the Lorenzo Hirsutism Scoring System) and acne were assessed 1, 3, 6, 9, and 12 months after randomization.

Risedronate increased posteroanterior spine BMD 3 % (95 % CI 1.8–4.6 %) compared with placebo (p < 0.0001), lateral spine BMD 4 % (95 % CI 1.9–5.6 %) compared with placebo (p = 0.0002), and hip BMD 2 % (95 % CI 0.4–3.4 %) compared with placebo (p = 0.013) in women with AN over the 12-month clinical trial. Testosterone administration did not improve BMD but increased lean body mass 1.9 % (95 % CI 0.2–3.6 %) compared with placebo (p = 0.037) and acutely stimulated bone formation, but had no significant effect on total body water or fat mass. There was no significant difference in the response of BMD to risedronate between the patients receiving testosterone coadministration and those receiving placebo patches. There were few side effects associated with either therapy.

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

Kommentit

Hoitoajat olivat lyhyitä (pisimmillään 1 vuosi) ja potilasmäärät pieniä. Bifosfonaatit vähentävät entisestään luun turnoveria AN-potilailla, ja niillä on pitkä kahdentumisaika. Tutkimukset bisfosfonaattien pitkäaikaisvaikutuksista ja erityisesti niiden mahdollisesta teratogeenisesta vaikutuksesta raskauden aikana ovat vähäiset (eläimillä on todettu haitallisia vaikutuksia). Bisfosfonaatit läpäisevät istukkaa, joten niiden käyttöä ei voida suositella laihuushäiriöpotilailla luukadon hoidossa. Lisäksi niiden vaikutuksesta murtumien ehkäisyssä ei ole olemassa tutkimuksia.

Kirjallisuutta

  1. Golden NH, Iglesias EA, Jacobson MS ym. Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab 2005;90:3179-85 «PMID: 15784715»PubMed
  2. Nakahara T, Nagai N, Tanaka M ym. The effects of bone therapy on tibial bone loss in young women with anorexia nervosa. Int J Eat Disord 2006;39:20-6 «PMID: 16231362»PubMed
  3. Miller KK, Meenaghan E, Lawson EA ym. Effects of risedronate and low-dose transdermal testosterone on bone mineral density in women with anorexia nervosa: a randomized, placebo-controlled study. J Clin Endocrinol Metab 2011;96:2081-8 «PMID: 21525157»PubMed