Jags 2008;56:935; Nejm 2008;358:1474; 2006;354:2250; 2005;353:595

Cause:

CAUSES OF OSTEOPOROSIS

• Acromegaly
• Alcoholism
• Anorexia (Ann IM 2000;133:790)
• Cushing's disease/syndrome (even 10 mg prednisone qd enough), including chronic steroid use even inhaled in asthmatics (New Eng J Med 2001;345:941) and rheumatoid arthritis (Ann IM 1993;119:963)
• Diabetes, type I
• Estrogen deficiency in postmenopausal women or amenorrheic athletes (New Eng J Med 1984;311:277); hypogonadotrophic hypogonadism in men
• Homocystinuria (New Eng J Med 2004;305:2033, 2042)
• Hyperparathyroidism
• Hyperthyroidism
• Idiopathic, at least some of which is genetic in structure of bone matrix protein (New Eng J Med 1998;338:1016)
• Malabsorption
• Myeloma
• Puberty, late onset, at least in men (New Eng J Med 1992;326:600)
• Renal calcium leak (rx'd w thiazides)
• Scurvy
• Vitamin A chronic excessive intake >3000 µgm/d (Jama 2002;287:2815; Ann IM 1998;129:770)
• Vitamin D winter time deficiency (Jama 1995;274:1683)
• Vitamin D antagonist meds like phenytoin

Pathophys:Estrogen deficiency postmenopausally; in athletes and other younger women, the problem is either the estrogen deficiency and/or progesterone deficiency from short or absent luteal phase (Nejm 1990;323:1221)

More in female smokers from changes in estrogen metabolism (Nejm 1994;330:387); less frequent in blacks and Polynesians because they start with higher adolescent bone densities (Nejm 1991;325:1597) and rates of loss are slower (Jags 2005;53:183). Osteopenia/-porosis present in 42%/7% of US women over age 50 yr (Jama 2001;286:2815)

Sx:Bone pain, esp vertebral; fractures

Si:Decreased height/kyphosis from vertebral compression fractures, measure w rib–pelvis distance 2 finger breadths (Jama 2004;292:2890)

Chronic, slowly progressive

Rib, extremity and vertebral fractures especially; many asymptomatic.

r/o causes listed above when premature, ie, in men under 70 yr and women under 60 yr

Lab:

Chem: PTH, serum and urine calciums to r/o hyperparathyroid and renal calcium leak in asx postmenopausal type (D. Spratt 9/95). Vit D levels by radio-immunoassay, 25-OH vit D <25 nm/L (Jags 2008;56:785); but little evidence that rx needed or beneficial for levels of 10-30 ng/cc (Cliff Rosen-Nejm 2011;364;248). In men: TSH, calcium, LFTs, creatinine/BUN, total testosterone, 25-OH vit D (treat levels <30 ng/cc)

FRAX score: WHO Fracture Risk Algorithm amalgamates risk factors including BMD to calculate a 10-year fracture risk in older adults (Osteoporosis Int 2005;16:581)

Xray:

Osteopenic bones and fractures

Screening (Osteoporosis)

Rx: (Nejm 2007;356:2293)

All preventive or instituted to slow the progression (Med Let 1992;34:101) and work to prevent the steroid-induced type as well (Nejm 1993;329:1406).

Weight-bearing exercise (Nejm 1996;124:187)

Smoking cessation; helps exercise and allows protective effect of estrogens (Ann IM 1992;116:716)

Calcium replacement therapy (Med Let 2000;42:29), as CaCO₃, 1-1.5 gm of elemental Ca⁺⁺/d; milk has 300 mg Ca⁺⁺ /cup; chewable Tums, 200 or 500 mg/tab; Oscal, 500 mg/tab; Ca citrate (Citracal) 315 mg/tab, but absorbed better, esp in pts on PPI/achlorhydrics/elderly (Nejm 1985;313:70); all come w 200+ IU vit D/500+ mg of Ca⁺⁺; $5-7/mo. Modest effect (Nejm 2006;354:669, 750; ACP J Club 2006;145:4)

Vitamin D as 600-800 IU qd or calcitriol (D₃) 0.25 µgm po bid may decrease falls and fractures without producing stones by preventing increased PTH of winter at least (Jama 2005;293:2257; Nejm 1993;327:1637; 1992;326:357; Ann IM 1991;115:505); other RCTs find no effect unless levels <10 ng/cc? (Nejm2011;364:248; 2006;354:669)

Bisphosphonates; can decr fx rate after hip fx (secondary prevention) (Nejm 2007;357:1799, 1861); 5 yr of rx enough since drug persists for years in the bone (Med Let 2008;50:69; Jama 2006;296:2927, 2968) and atypical femoral shaft fx rates incr × 3 after 4-5 yr (Jama 2011;305;783) and absolute risk low, benefits > risks (Nejm 2011;364:1728). Adv effects: osteonecrosis (Med Let 2007;49:89; Nejm 2006;355:2278; Jama 2006;295:2833; Ann IM 2006;144:753) of jaw > mandible > maxilla, esp with dental disease or extractions (get all repairs done before start) and w iv preparations; costs and risks outweigh benefits in merely osteopenic pts unless other risk factors (Ann IM 2005;142:734, 796); all around $1100/yr except for generic alendronate

• Alendronate (Fosamax) (Med Let 2001;43:26) 70 mg q 1 wk clearly helps prevent progression over 10 yr, NNT-3 = 10-30 (Nejm 2004;350:1189), or 35 mg q 1 wk for prevention in osteopenic and/or high-risk women (eg, on steroids); adverse effects: various gi sx, rarely chemical esophagitis esp if not taken w lots of fluids and pill sits on esophageal mucosa (Nejm 1996;335:1016)
• Risedronate (Actonel) (Med Let 2002;44:87; Jama 1999;282:1344) 2.5-5 mg po qd, or 35 mg/wk; decr hip fx in elderly women, NNT-3 = 90 (Nejm 2001;344:333) vs NNT-1 = 12 (Jags 2004;52:1832)
• Ibandronate (Boniva) (Ann Rheum Dis 2006;65:654) 2.5 mg po qd, or 150 mg po q 1 mo or 3 mg iv q3mo; must stand for 60 min after take. Data only supports use for vertebral fxs (HMS 3/06)
• Pamidronate (Aredia), esp if on steroid or leuprolide (Nejm 2001;345:948) rx; 60 mg iv q 3-12 mo
• Zoledronate (Reclast) (Nejm 2007;357:1799, 1861; Med Let 2007;49:89) 5 mg iv q 12 mo; like generic pamidronate but infuses over 15 min unlike 2 h w pamidronate

Calcitonin (Cibacalcin) 100 IU sc/im or 200 IU nasally qd; also relieves acute fx pain possibly via opiate effect (J Fam Pract 1992;35:93), not as good as alendronate (J Clin Endocrinol Metab 2000;85:1783); nasal $60/mo, sc/im $225/mo

Parathyroid hormone teriparatide (Forteo) (Jags 2006;54:782, 853) sc daily either as 40 µgm of the 34 aa fragment, or 100 µgm of the full 84 aa PTH, NNT = 10 (ACP J Club 2006;145:71); no fx outcome studies, effects inhibited by concurrent bisphosphonate rx (Nejm 2003;349:1207, 1216, 1277), perhaps alternate q q3mo$7000/yr

Osteoclast receptor blockers: denosumab (Prolia) (J Clin Endocrinol Metab 2011;96: doi:10.1210, Nejm 2009;361:745, 756, 818) 60 mg sc q 6 mo dramtically decr fx rate in women w T score <2.5 and men on androgen deprviation rx. Adv effects: immunosuppression

Hormonal w selective estrogen receptor modulators (p 515) like raloxifene (Evista) et al; or androgens in men if hypogonad perhaps

Vertebroplasty w polymethylmethacrylate (J Neurosurg 2003;98:36; Clin Ger 2004;12:32;Spine 2006;31:57) vs no benefit by DBCT (Nejm 2009;361:557, 569, 619)

Statin drug rx of incr cholesterol also helps slow osteoporosis? (Jama 2000;283:3205, 3211, 3255; Lancet 2000;355:2185 vs Ann IM 2003;139:97; Jama 2001;285:1850)

Thiazides help bone density and fx rate (Ann IM 2003;139:476; 2000;133:516) w/o adverse lipid effects (Jags 2003;51:340) as do -blockers (Jama 2004;292:1326)

Folic acid 5 mg po qd and B₁₂ 1500 µgm po qd to lower homocysteine levels (Nejm 2004;350:2033, 2042, 2089) and fx rates (NNT = 14) (Jama 2005;293:1082, 1121)