ADVANCES IN WOMEN’S HEALTH: OSTEOPOROSIS/GENITAL INFECTIONS
| NEW ERA IN OSTEOPOROSIS MANAGEMENT —Michael D. Whitaker, MD, Consultant in Endocrinology,
Mayo Clinic Scottsdale, Arizona
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| Background: osteoporosis expected eventually to result in fracture in 50% of white women; hip fracture mortality 25%
within 1 yr; leads to long-term nursing care; bone mass in women peaks at 30 to 35 yr of age; bone loss 2% to 4% per
year during 5 to 8 yr of perimenopause and early menopause; by 90 yr of age, women have lost 50% of skeleton
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| Bone physiology: constantly remodeling; cyclic stages—quiescence; osteoclasts migrate to trabecular bone (become
activated; resorb bone for ≈2 wk, leaving holes; apoptosis occurs); osteoblasts recruited (begin bone formation, refilling
holes); after 3 mo, new stage of quiescence begins; normal cycle—resorption and formation tightly coupled and
equal; osteoporosis—with aging and menopause, cycle speeds up; resorption and formation coupled inefficiently;
formation lags behind resorption, leading over time to bone loss
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| Goal of therapy: to prevent fractures
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| Nonpharmacologic interventions: probably more important than any drug
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 | Calcium: 1500 mg per day
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| Vitamin D: deficiency endemic in United States, “even in Arizona and South Florida”; current recommended daily
allowance (RDA) 400 U (soon to be 800 U); speaker recommends ≥800 to 1000 U per day; when vitamin D low,
calcium not absorbed properly, stimulating parathyroid hormone (PTH) production and increasing bone turnover
(disrupts remodeling cycle, causing bone loss)
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| Exercise: physical therapy mobilizes women with multiple vertebral fractures; weight-bearing exercise needed to
prevent bone loss
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| Life factor modification: eg, smoking and alcohol intake
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| Physical stress: avoidance most important; biggest single cause of fractures; requires 2 things to break bone; first,
low bone density; second, apply stress to bone; avoid risky activities, eg, downhill skiing, golf
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| Pharmacologic therapy: only 2 targets; 1) shut off osteoclasts to prevent resorption; 2) affect osteoblasts to speed
bone formation; without treatment—bone loss continues; bone density eventually passes fracture threshold and
fractures increase
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| Antiresorptive therapy: does not build new bone; strengthens bone by reducing bone turnover and allowing mineralization;
drugs that decrease bone resorption—estrogens; bisphosphonates; raloxifene and calcitonin (less potent
than bisphosphonates; useful in selected patients)
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| Bisphosphonates: alendronate (Fosamax); risedronate (Actonel); ibandronate (Boniva); studies show almost 50%
decrease in rate of vertebral, hip, and wrist fractures (hip fracture data less firm for newest, ibandronate); inside
bone, drugs “last forever,” suggesting less frequent dosing required (once-monthly dose of ibandronate affects
bone density same as once-daily)
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| Patient adherence poor: even with once-weekly dose, after 12 mo, <50% of women taking alendronate or risedronate
properly; while fracture rate reduced in adherent patients, rate increased 25% in nonadherent; alternative
dosing strategies—may improve adherence; study comparing daily alendronate with monthly ibandronate found
71% preferred monthly dose; potential for more convenient dosing seen in study of drug not currently indicated
for reducing fractures (zoledronic acid [Zometa] increased bone density over 1 yr, whether infused at rate of 1-
mg dose every 3 mo, 2-mg dose every 6 mo, or single 4-mg dose yearly; study of effect on fracture reduction under
way); intravenous (IV) injection of ibandronate (2 mg every 2 mo or 3 mg every 3 mo) under consideration
by Food and Drug Administration (FDA)
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| Formation stimulation therapy: build new bone; teriparatide (Forteo)—PTH analogue; placebo-controlled study
using 20-µg dose found vertebral fracture rate reduced 65% (1600 menopausal women with ≥1 vertebral fracture
followed for median of 21 mo); risk of other fractures (eg, hip, wrist, rib) reduced >50%
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| Combination therapy: antiresorptive and anabolic therapy; alternative strategies—giving alendronate and Forteo
at same time resulted in blunting of effect of Forteo; when Forteo given for 1 yr and stopped, gains in bone density
lost in patients put on placebo and maintained in patients given Forteo and alendronate; cyclic dosing (alternating
Forteo alone for 3 mo with alendronate alone for 3 mo; bone density increase same as giving Forteo
daily); another study found similar benefits alternating Forteo and alendronate therapy at 1-yr intervals
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| Summary of combination therapy options: stopping antiresorptive and adding anabolic (probably helpful); giving
antiresorptive with anabolic (not indicated); taking anabolic (PTH) with raloxifene or hormone replacement therapy
(HRT; may be synergistic); alternating PTH with either alendronate, raloxifene, or HRT (beneficial); PTH
taken only for 18 to 24 mo
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| Questions and answers: follow-up dual energy x-ray absorptiometry (DEXA) scanning—get baseline; wait 12 to 18
mo (device unable to detect changes any sooner); how long to continue bisphosphonates—currently uncertain; perhaps
after 8 to 9 yr, alendronate could be discontinued for 1 to 2 yr without bone loss (speaker’s practice); other bisphosphonates
less long-lasting; other recommendations for DEXA screening—after gastric bypass (when patients
lose enough weight to fit on table; otherwise, measure at wrist; bone loss results from vitamin D deficiency); prostate
cancer (androgen deprivation therapy requires careful screening)
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| CONTEMPORARY MANAGEMENT OF GENITAL TRACT INFECTIONS —Michael S. Policar, MD, Associate
Clinical Professor of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco,
School of Medicine
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| Prevention issues: included in Centers for Disease Control and Prevention (CDC) 2006 guidelines; advising patients
which sexually transmitted diseases (STDs) being tested for (eg, test for gonorrhea, Chlamydia trachomatis, and
human papillomavirus [HPV] included with Papanicolaou [Pap] test); routine sexual-history taking and risk-reduction
counseling; nonoccupational postexposure prophylaxis for HIV (eg, after sexual assault); availability of emergency
contraception; counseling to avoid douching and excessive use of nonoxynol-9 spermicides
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| Herpes simplex virus (HSV)-2 serologic testing: use accepted in symptomatic patients, but controversial as screening
test in asymptomatic
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| Guidelines for screening: issued by California CDC branch; should not offer—to general population; during pregnancy;
should offer—to HIV-positive patients; discordant couples (verify status of uninfected partner); patient at
risk for STDs (if he or she wants to know in order to change behavior); study found valacyclovir therapy in infected
partner for 1 yr reduced rate of transmission only 2% (up to patient to decide if therapy worthwhile)
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| Treatment: valacyclovir 500 mg qd; indications—discordant couples (check uninfected partner annually); infected
patient with multiple partners; men who have sex with men; HIV-infected patients
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| HPV testing: clinically useful for—triage of women with atypical squamous cells of undetermined significance (ASCUS)
Pap tests; in coscreening (HPV and Pap) in women >30 yr of age (if negative for both, Pap test not indicated
for 3 yr); follow-up of low grade squamous epithelial lesions (LSIL) in untreated adolescents; postcolposcopy and
posttreatment follow-up (in lieu of Pap test); no proven benefit—triage of patients with Pap tests that show high-
grade squamous intraepithelial lesions (HSIL), atypical squamous cells suggestive of HSIL (ASC-H), LSIL, and
atypical glandular cells (AGC); STD screening in general population; evaluation of sex partners or evaluation of
genital warts; test only for high-risk HPV types
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| Vaginal trichomoniasis treatment: metronidazole (MTZ) 2 g, 1 dose po; new addition—tinidazole (Tindamax) 2 g,
1 dose; alternative—MTZ 500 mg bid for 7 days; comments—generic MTZ much less expensive than Flagyl;
tinidazole—more expensive than MTZ; recommended following MTZ failure and for patients intolerant to MTZ
side effects (but not true allergy); tips—advise patients trichomoniasis could be transmitted by any partner during
lifetime; use fresh saline solution for detecting trichomonads under microscope (older solutions become hypertonic
and kill organism; dead organisms cannot be seen on wet mount); MTZ or tinidazole not contraindicated during
pregnancy
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| Bacterial vaginosis (BV): pathogenesis—loss of normal Lactobacillus opens way for overgrowth of anaerobes,
leading to discharge and malodor; treatment—MTZ 500 mg po for 7 days; MTZ vaginal gel; clindamycin
cream; alternative regimens—1-dose MTZ 2 g no longer recommended; (clindamycin 300 mg po bid for 7 days;
clindamycin ovules 200 mg per vagina qhs for 3 days); recurrent BV—≥3 episodes per year; occurs in 33% of
women with BV; treatment MTZ gel 0.75% bid for 10 days, then twice weekly as maintenance therapy; treatment
tradeoff—side effects and lower cost of MTZ vs expense, longer treatment duration, and fewer side effects
of topicals
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| Diagnostic tips: ≥20% of epithelial cells are clue cells; amine (“whiff”) test positive when odor changes after KOH
added to residue on posterior blade of speculum; vaginal pH 4.5 to 6.0; no role for vaginal culture or Pap test
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| Vulvovaginal candidiasis (VVC): uncomplicated—80% to 90% of cases; sporadic; mild; likely Candida albicans;
in immunocompetent women; complicated—recurrent; severe; non-albicans candidiasis; in immunocompromised
women (eg, uncontrolled diabetes, HIV infection, drug-caused immunosuppression, pregnancy); treat
more aggressively; treatment alternatives—topical cream or suppository for 3 or 7 days; fluconazole (Diflucan)
150 mg, 1 tablet po; after treatment failure—reconfirm diagnosis; treat with alternative antifungal drug; after repeated
failures—obtain candidal culture; non-albicans species may require different drug
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| Severe VVC: characterized by erythema, excoriation, and fissures); treat with topical therapy (7-14 days) or with
fluconazole 150 mg po at 3-day intervals (either 2 or 3 doses, depending on severity)
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| Candida glabrata vaginitis: causes burning rather than itching; diagnosis by culture or microscopy (see spores not
pseudohyphae); treatment options—terconazole for 7-14 days; boric acid capsules; topical gentian violet once
weekly for 3 wk; but not oral fluconazole
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| Recurrent VVC: ≥4 episodes per year; predisposing condition uncommon; partners rarely source of infection (most
vaginal yeast infections caused by same species of yeast as found in woman’s gut); use culture to confirm non-
albicans species); treatment options—early self-treatment regimen; or new suppressive regimen—3 doses of
fluconazole 150 mg po in 72 hr, then maintenance therapy with fluconazole 100 or 150 mg tablet once or twice
weekly; maintenance alternatives (itraconazole; clotrimazole suppositories once weekly; boric acid suppositories
twice weekly; gentian violet once monthly)
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| Diagnostic tips: 66% of women who think they have chronic or recurrent yeast infection actually do not; verify
diagnosis with polymerase chain reaction (PCR) testing or fungal culture; therapy with oral or vaginal yogurt
ineffective (different Lactobacillus species that cannot adhere to vaginal epithelial cells)
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| Routine screening for chlamydia: recommended in sexually active women through 25 yr of age at average or high
risk of genital tract infection (also for cervical gonorrhea, but only if prevalence ≥1% at screening site; for HIV in
drug users; offered to pregnant women); reason for emphasis on chlamydia—90% of infections undetected, untreated,
and mostly asymptomatic; sequelae include pelvic inflammatory disease (PID), ectopic pregnancy, chronic
pelvic pain, and infertility; prevalence 3% to 15% in sexually active teens; risk factors include age (15-25 yr), unprotected
sex, new or multiple sex partners, oral contraceptive use, and douching; study that compelled screening
for chlamydia—found 56% reduction in PID following screening and treatment
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| Questions and answers: HSV-1 infection—responsible for oral herpes; ≤50% of new genital infections found to be
HSV-1; population now entering sexual activity often lack immunity to HSV-1 from childhood cold sores, leading
to oral-to-genital transmission; screening recommendations (for HSV-2 alone) likely to change; hepatitis B
and C—CDC public health approach not case-finding but vaccination; offer concerned patient vaccination
rather than testing
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Educational Objectives
| The goal of this program is to educate internists about the management of osteoporosis and genital tract infections in
women. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Describe the bone remodeling cycle and how its disruption leads to osteoporosis.
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| 2. Counsel patients on nonpharmacologic methods they can adopt to prevent fractures from osteoporosis.
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| 3. Prevent osteoporotic fractures with antiresorptive and formation-stimulation drug therapies.
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| 4. Apply recommendations for screening and testing for genital tract infections in women.
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| 5. Treat genital tract diseases in women, including herpes simplex virus (HSV) -2 infection, trichomoniasis, bacterial
vaginosis, and chlamydia.
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Discussed on This Program
Alendronate sodium [Fosamax]
Boric acid
Calcium (several trade names and formulations) Calcitonin-salmon [Calcimar, Fortical, Miacalcin, Osteocalcin,
Salmonine]
Clindamycin [Cleocin, Cleocin Phosphate, Cleocin T, Clindagel, ClindaMax, ClindaMax Lotion, Clindesse,
Clindets]
Clotrimazole vaginal suppositories [Clotrimazole Combination Pack; Gyne-Lotrimin 3 Combination Pack, Mycelex-
7 Combination Pack
Fluconazole [Diflucan]
Gentian violet (methylrosaniline chloride; crystal violet) Ibandronate sodium [Boniva]
Itraconazole [Sporanox] Metronidazole [Flagyl, Flagyl 375, Flagyl ER, Metric 21, MetroCream, MetroGel,
MetroGel-Vaginal, MetroLotion, Noritate, Protostat]
Raloxifene [Evista]
Risedronate sodium [Actonel] Terconazole [Terazol 3, Terazol 7]
Teriparatide acetate (rDNA origin; parathyroid hormone) [Forteo]
Tinidazole [Tindamax]
Valacyclovir HCl [Valtrex] Vitamin D Zoledronic acid [Zometa]
Suggested Reading
Black DM et al: The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis.
N Engl J Med 349:1207, 2003; Cosman F et al: Daily and cyclic parathyroid hormone in women receiving
alendronate. N Engl J Med 353:566, 2005; Cosman F: The prevention and treatment of osteoporosis: a review.
MedGenMed 7:73, 2005; Hodsman AB et al: Parathyroid hormone and teriparatide for the treatment of osteoporosis:
a review of the evidence and suggested guidelines for its use. Endocr Rev 26:688, 2005; Epub 2005 Mar 15. Review.
Lecart MP et al: Combination/sequential therapy in osteoporosis. Curr Osteoporos Rep 2:123, 2004; Mammen-Tobin
A et al: Management of metronidazole-resistant Trichomonas vaginalis--a new approach. Int J STD AIDS 16:488,
2005; McCarus DC: Fracture prevention in postmenopausal osteoporosis: a review of treatment options. Obstet Gynecol
Surv 61:39, 2006; Nyirjesy P et al: Vulvovaginal candidiasis. Obstet Gynecol Clin North Am 30:671, 2003; Patel
DA et al: Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy:
results of a prospective cohort study. Am J Obstet Gynecol 190:644, 2004; Reginster JY et al: The treatment of severe
postmenopausal osteoporosis: a review of current and emerging therapeutic options. Treat Endocrino l5:15,
2006; Schwebke JR et al: Risk factors for bacterial vaginosis in women at high risk for sexually transmitted diseases.
Sex Transm Dis 32:654, 2005; Seeman E: Alendronate and vertebral fracture risk. Mayo Clin Proc 80:1236, 1238;
author reply 1238, 1240, 2005; Sobel JD et al: Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis.
N Engl J Med 351:876, 2004; Sobel JD: Current trends and challenges in candidiasis. Oncology (Williston Park)
18:7, 2004; Sobel JD: What's new in bacterial vaginosis and trichomoniasis? Infect Dis Clin North Am 19:387, 2005;
Solomon DH et al: Compliance with osteoporosis medications. Arch Intern Med 165:2414, 2005; Wilson JD et al:
Recurrent bacterial vaginosis: the use of maintenance acidic vaginal gel following treatment. Int J STD AIDS 16:736,
2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following
has been disclosed: Dr. Whitaker—Eli Lilly (research grant).
Dr. Whitaker was recorded at the 8th Annual Mayo Clinic Internal Medicine Update: Sedona 2005, sponsored by
Mayo Clinic College of Medicine and Mayo School of Continuing Medical Education, Scottsdale, Arizona, and held
in Sedona, Arizona, October 6-9, 2005; Dr. Policar, at 20th Annual Primary Care Medicine: Principles & Practices,
sponsored by the University of California, San Francisco, School of Medicine, Department of Medicine, Division of
General and Internal Medicine, and held in San Francisco, October 19-21, 2005. The Audio-Digest Foundation
thanks the speakers and the sponsors for their cooperation in the production of this program.
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