1. Assess fracture risk and determine need for conservative and medical management of osteopenia and osteoporosis.

2. Discuss the benefits and adverse effects associated with treatment options for patients with osteoporosis.

3. Define CPP and discuss potential contributing factors.

4. Detail the differential diagnosis for CPP.

5. Diagnose and treat women with endometriosis and other conditions that contribute to CPP.

Osteoporosis
Michael Bruderly, MD, Medical Director, Ann Arbor Family Practice, IHA, and Family Physician, Department of Family Medicine, St. Joseph Mercy Hospital, Ann Arbor, MI

Incidence and impact: 50% of women 50 yr of age have low bone mass, 10% to 20% have frank osteoporosis; high lifetime risk for osteoporotic fractures (annually outnumber heart attacks, strokes, and breast, uterine, and ovarian cancers combined); outcomes—after hip fracture, 1-yr mortality 15% to 20%; only 30% of patients with osteoporotic fracture return to baseline function; underdiagnosis—low rates of screening, diagnosis, and treatment of osteoporosis, even after fracture; treatment often inadequate

Diagnosis: dual energy x-ray absorptiometry (DEXA) used to calculate bone mineral density (BMD); BMD of individual compared to control of same sex at younger age (T score); BMD of patient compared to age- and sex-matched control (Z score); diagnostic criteria—T score <-2.5 or history of fragility fracture (presence of both indicates severe osteoporosis)

Decision to treat: based on risk for fracture, T score, and age; age independently affects risk (increases risk for falls; associated with qualitative changes in bone architecture); controversy about treating patients with osteopenia (not cost-effective among women 55-75 yr of age); however, most fractures occur in women with osteopenia; treatment appropriate in many older women with osteopenia (consider fracture risk, mobility, goals, and life expectancy); comorbid conditions—may exacerbate bone loss and increase risk (not reflected in Z score); diagnosis cost-effective, since identification may affect management

Exercise: weight-bearing; effects disappear ≤1 yr after discontinuation; moderate impact and intensity sufficient; high-intensity exercise that results in weight loss may increase risk for fracture; fracture risk decreases with increasing duration of exercise (plateaus after 4 hr/wk); recommended for all patients without contraindication

Calcium and vitamin D: supplementation slows bone loss by 1% to 2% at all sites and decreases risk for vertebral fractures by ≈20%; vitamin D may have added benefit of reducing risk for falls; combination appropriate for prevention but insufficient as monotherapy for osteoporosis; calcium—daily intake should not exceed 2500 mg (use calcium intake assessment forms to estimate dietary intake and need for supplementation); higher daily intake may increase risk for constipation, dyspepsia, and nephrolithiasis; calcium citrate absorbed better than calcium carbonate (especially in presence of antireflux therapy) and preferred for patients with anemia; patients requiring \>600 mg/day should divide dose to maximize absorption; vitamin D—recommended daily intake, 800 U; high doses (>2000 U) for prolonged period may cause toxicity; most patients have low daily intake

Hormonal therapies: estrogen—approved for prevention of osteoporosis; also effective as treatment; associated with 34% decrease in all fractures among women with relatively low risk; requires continued use (bone loss increases after discontinuation), but continuous therapy increases other risks; generally reserved for patients with severe osteoporosis with few alternatives for treatment; raloxifene—selective estrogen-receptor modulator (SERM) approved for prevention and treatment; BMD increases by ≈2%; risk for vertebral fracture decreases by 30% to 40%, but little effect on nonvertebral fractures; adverse effects include hot flushes, cramps, and deep venous thrombosis (1 in 160 women); probably less effective than bisphosphonates; combination therapy with bisphosphonates improves BMD but not risk for fracture; may have protective effect against breast cancer; calcitonin—inhibits osteoclasts, reducing resorption of bone; administered nasally; approved for treatment but also effective for prevention; effects similar to those of raloxifene; adverse effects include nasal congestion, nausea, and flushing (effects mitigated by taking antihistamine 30 min before calcitonin); potentially antigenic; recommended as treatment for pain after vertebral fracture (reduces pain scores by 50% 1-2 mo after fracture); not appropriate as monotherapy for osteoporosis

Bisphosphonates: preferred therapy; increase BMD and decrease risk for vertebral and nonvertebral fractures; alendronate—associated with slightly better gains in BMD, compared to other agents, but no difference in fracture risk; ibandronate—once-monthly dosing; reduced risk for nonvertebral fractures only among patients with severe osteoporosis; other effects similar to those of alendronate; zoledronate—once-yearly intravenous (IV) infusion, associated with impressive decreases in vertebral fractures; adverse effects include bone pain, decreased serum levels of calcium, and increased rate of atrial fibrillation (trend seen among all bisphosphonates); compliance—≈50% at 1 yr, regardless of dosing regimen; adverse effects—generally well tolerated; gastric irritation reduced when taken on empty stomach with 8 oz water; patient should remain upright for 30 to 60 min after dosing; contraindications include low serum levels of calcium, inability to remain upright, active gastrointestinal (GI) problems, and creatinine clearance <35 mL/min; caution required in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) and those with history of GI problems; osteonecrosis rare, and typically associated with high-dose rapid infusions used in cancer therapy; how long to use—alendronate half-life 10 yr; study showed protective effect persisted 5 yr after discontinuing therapy, although effect not as great as when therapy continued; those who stopped had increase in markers of bone turnover (but not to pretreatment levels) and clinical increase in vertebral fractures; continued therapy associated with 3.5% higher BMD; drug holiday acceptable in many patients, but monitoring of bone-turnover markers recommended

Teriparatide: anabolic therapy; recombinant parathyroid hormone stimulates formation of bone and restores microarchitecture; daily injection; greater improvements in BMD and fracture risk than with bisphosphonates; adverse effects include dizziness and cramping; black box warning due to increased incidence of osteosarcoma (in rats); limited data on optimal duration of therapy; used only in patients with severe osteoporosis

Combination and sequential therapies: teriparatide plus bisphosphonate—no added benefit; bone turnover may increase; bisphosphonates may blunt anabolic effect of teriparatide for ≤6 mo after use; teriparatide followed by bisphosphonate—associated with additional gains in BMD; no data on fracture rates

Monitoring response: no evidence for benefit associated with follow-up DEXA; difference between bone turnover markers at baseline and at 6 mo gives indication of treatment response (consider DEXA if markers decrease <50%); no treatment alternatives for patients in whom therapy unsuccessful; BMD—imperfect surrogate for fracture risk; measurements highly variable (especially when taken from different machines); baseline BMD more predictive of fracture risk than changes in BMD over time

Chronic Pelvic Pain
Anita L. Nelson, MD, Professor of Obstetrics and Gynecology, the David Geffen School of Medicine at the University of California, Los Angeles, and Harbor-UCLA Medical Center, Los Angeles

Definitions: general issues—multiple organs may contribute to chronic pelvic pain (CPP); pain may be referred from areas outside pelvic region; onset and timing of pain may give clues to etiology; American College of Obstetricians and Gynecologists (ACOG) criteria—noncyclic pain, lasting ≥6 mo, isolated to anatomic pelvis (includes anterior abdominal wall at or below umbilicus, lumbosacral region, buttocks, and vulva) and causing functional disability

Components of pain: physical and psychologic components contribute to pain experience; psychologic factors affect processing of pain signals in brain; pain causes changes in muscle tone and hormone function, which may lower threshold for pain, increasing sensitivity to and interpretation of pain and nonpain signals; gate-control theory—peripheral nerve sends pain signal (may originate from variety of nerve fibers); transmission of signal from spinal cord to brain dependent on status of gate; pain syndromes may result from malfunctioning gates; peripheral and central influences affect status of gate

Contributing factors: mood (eg, depression, anxiety); neurotransmitter abnormalities common to pain syndromes and to depression; altered neural connections in spinal cord may lead to misinterpretation of benign stimuli; women with CPP have higher density of pain fibers in lower uterine segment (despite normal anatomy and histology); chronic pain can alter neuroanatomy and neurophysiology of spinal cord; hypersensitivity—women with CPP require larger doses of analgesics after surgery and more anesthetic to numb area before biopsy; preoperative dose of gabapentin reduces postoperative pain 30 days after surgery

Reliability of findings: absence of physical findings does not eliminate need for follow-up; 10% to 30% of women with abnormal pelvic examinations have no abnormal findings on laparoscopy; \>50% of women with abnormal laparoscopic findings had normal preoperative examinations

Sources of CPP: reproductive system; genitourinary system; GI system (including anatomic and functional abnormalities); musculoskeletal system (including arthritis and occult fractures); women with \>1 etiology typically have greater pain scores, lower pain thresholds, more constant pain, and more pain-related problems, eg, dysmenorrhea, dyspareunia

Prevalence and impact: 15% to 20% of women have ≥1 yr of CPP during reproductive years; common reason for laparoscopy; ≥1 in 10 hysterectomies performed in effort to treat CPP (often fails); diagnosis and treatment—≈20% of women with CPP seek treatment from gynecologists; ≈10% seek treatment from other clinicians; ≈66% self-treat; 61% of women who seek care receive no diagnosis; common diagnoses include endometriosis, pelvic inflammatory disease (PID), and yeast infections; factors that do not affect risk—age (affects etiology but not incidence); ethnicity; education; economic status; risk factors—history of physical or sexual abuse; posttraumatic syndromes; history of PID, endometriosis, or interstitial cystitis; pregnancy; musculoskeletal conditions; mood disorders; multiple contributing factors—treatment may require multiple modalities; incomplete response does not indicate treatment failure

History: pain—complete description, including onset and patterns; pain diary may be useful; previous evaluation and treatments—types; efficacy; impact—fears; functional limitations; possible secondary gain; other relevant history— menstruation and its effect on pain; surgery; psychologic disorders; identification of depression

Pain assessment: International Pelvic Pain Society pelvic pain assessment tool; ask patients to rate pain during examination

Physical examination: complete physical examination to identify nongynecologic sources of pain (eg, arthritis, low back pain, headache, thyroid abnormalities, costochondritis); history of substance abuse or frequent use of NSAIDs warrants assessment of liver function; abdominal examination—rule out masses; palpate abdomen while patient lying on back (relaxed); assess severity and location of pain; repeat examination while patient contracts abdomen (half sit-up, unsupported); increased tenderness with contraction indicates problem with abdominal wall; intraperitoneal tenderness generally decreases with abdominal contraction; psoas and piriformis—pain with hip extension indicates psoas; pain with internal rotation (against resistance) indicates piriformis; once source identified, trigger point injections may alleviate pain; pelvic examination—check for vestibulitis; if patient has difficulty relaxing, instruct her to hold contraction (as in Kegel exercise); introduce instrument upon fatigue; palpate and milk urethra before introducing speculum; check for vaginismus and urethral tenderness; check for cervical motion tenderness by slowly moving cervix from side to side; squeeze bladder separately (looking for interstitial cystitis); palpate pelvic floor; elevate and compress uterus; perform rectal examination

Endometriosis: cyclic exacerbation of pain (but may have chronic element); dysmenorrhea common, often beginning 2 to 3 days before onset of bleeding; pre- or postmenstrual spotting may occur; menstrual bleeding often heavy and prolonged; pain may extend beyond pelvis; urinary frequency and thrust dyspareunia may occur; implants in bladder or bowel may cause bleeding into those organs; chronic recurrent disease requires convenient long-term therapy with few adverse effects and low cost; diagnosis and treatment—laparoscopy may not identify patients with nonclassical findings; surgery only if medical therapies fail; pain recurs in 40% of patients after surgical excision

Medical therapies: oral contraceptives cause pseudopregnancy (soften implants and prevent progression); leuprolide (Lupron) induces pseudomenopausal state (expensive; approved only for ≤6 mo); aromatase inhibitors (eg, letrozole) appropriate for women at high risk for breast cancer (block estrogen receptors and shut down production of estrogen); subcutaneous medroxyprogesterone (eg, Depo-Provera) as effective as gonadotropin-releasing hormone (GnRH) agonists at reducing pain associated with endometriosis and causes less bone loss; levonorgestrel intrauterine system (LNGIUS) useful for women with implants in rectum and vagina but not ovaries

Irritable bowel syndrome (IBS): functional disorder with increased sensitivity to visceral stimuli; prevalence—10% to 15%, but only one-third of these seek treatment; key to diagnosis—symptoms improve after defecation; colonoscopy findings often normal; management—stop smoking; avoid caffeine; elevate feet while defecating; consider fiber (no effect on pain, but may help constipation) or osmotic laxatives

Interstitial cystitis: bladder pain but no evidence of infection; diagnosis—pelvic pain, urgency, and frequency (PUF) score \>15 (95% predictive when score \>20); nocturia common; prevalence—more common among women; often presents just before menopause; commonly misdiagnosed; etiology—abnormal bladder epithelium; neural up-regulation increases pain sensitivity; examination and laboratory tests—squeeze bladder; perform urinalysis; administer PUF questionnaire; consider potassium sensitivity test or empiric treatment for patients with low PUF score but high index of suspicion; treatment—infuse bladder with mixture of lidocaine and heparin or bicarbonate; avoid hydrodistention; encourage bladder training, dietary changes, stress management, and physical therapy; manage expectations

Fibromyalgia: all quadrants of body and axial skeleton affected; diagnosis requires tenderness at ≥11 of 18 points; peripheral sensory stimuli misinterpreted as pain

Psychologic disorders: somatization disorder—multiple physical complaints; diagnosis requires ≥4 sites of pain, including non-GI pain; overlap with fibromyalgia and IBS; other disorders—hypochondriasis; substance abuse; factitious disorders; malingering

Other sources of CPP: urethral syndrome (treat with doxycycline); hernia; disc disease; poor posture

Newer therapies: nerve stimulation—transcutaneous electrical nerve stimulation; posterior tibial nerve stimulation approved for treating bladder irritability, urge incontinence, and pelvic pain; botulinum toxin (BOTOX)—injecting 80 U (under awake sedation) to muscles of pelvic floor reduces abnormal contractions and improves pelvic pressure scores