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Osteoporosis

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SOURCE

Source: O’Connell MB, Borchet JS. Osteoporosis and Osteomalacia. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146068952. Accessed May 19, 2017.

DEFINITION

  • Bone disorder characterized by low bone mineral density (BMD), impaired bone architecture, and compromised bone strength predisposing to increased fracture risk.

ETIOLOGY

  • Genetics.

  • Diet.

  • Lifestyle.

  • Hormonal status.

  • Diseases.

  • Medications (Table 1)

  • Aging.

TABLE 1.Select Medications Associated with Increased Bone Loss and/or Fracture Risk
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TABLE 1. Select Medications Associated with Increased Bone Loss and/or Fracture Risk
Medications Comments
Anticonvulsant therapy (phenytoin, carbamazepine, phenobarbital, and valproic acid) ↓ BMD and ↑ fracture risk; increased vitamin D metabolism leading to low 25(OH) vitamin D concentrations

Antiretroviral therapy (ART)

 Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) (zidovudine, didanosine, lamivudine, and tenofovir)

 Protease inhibitors (PI) (nelfinavir, indinivir, saquinavir, ritonavir, and lopinavir)

 ↓ BMD (NRTIs > PI), no fracture data; increased osteoclast activity and decreased osteoblast activity
Aromatase inhibitors (eg, letrozole and anastrozole) ↓ BMD and ↑ fracture risk; reduced estrogen concentrations
Canagliflozin ↓ BMD and ↑ fracture risk (FDA reviewing SLGT2 inhibitor class of medications)
Furosemide ↑ fracture risk; increased calcium renal elimination
Glucocorticoids (long-term oral therapy) ↓ BMD and ↑ fracture risk; increased bone resorption and decreased bone formation; dose and duration dependent; see special populations section
Gonadotropin-releasing hormone agonists or analogs (eg, leuprolide and goserelin) ↓ BMD and ↑ fracture risk; decreased sex hormone production
Heparin (unfractionated, UFH) or low molecular weight heparin (LMWH) ↓ BMD and ↑ fracture risk (UFH >>> LMWH) with long-term use (eg > 6 months); decreased osteoblast replication and increased osteoclast function
Medroxyprogesterone acetate depot administration ↓ BMD, no fracture data; possible BMD recovery with discontinuation; decreased estrogen concentrations
Proton pump inhibitor therapy (long-term therapy) ↓ BMD and ↑ fracture risk; possible calcium malabsorption secondary to acid suppression for carbonate salts
Selective serotonin reuptake inhibitors ↓ BMD and ↑ fracture risk; decreased osteoblast activity
Thiazolidinediones (pioglitazone and rosiglitazone) ↓ BMD and ↑ fracture risk; decreased osteoblast function
Thyroid—excessive supplementation ↓ BMD and ↑ fracture risk; risk increases with TSH concentration < 0.1 mIU/L; possible increase in bone resorption
Vitamin A—excessive intake (> 1.5 mg of retinol form) ↓ BMD and ↑ fracture risk; decreased osteoblast activity and increased osteoclast activity

BMD, bone mineral density; TSH, thyroid-stimulating hormone; DXA, dual-energy X-ray absorptiometry.

Reprinted with permission from DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017.

PATHOPHYSIOLOGY

  • Men and women begin to lose bone mass starting in third or fourth decade because of reduced bone formation.

  • Estrogen deficiency during menopause increases osteoclast activity, increasing bone resorption more than formation.

  • Etiology of male osteoporosis ...

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