Vertebral fracture

A major regulator of bone metabolism and calcium homeostasis, parathyroid hormone (PTH) is stimulated through a decrease in plasma ionised calcium and increases plasma calcium by activating osteoclasts. PTH also increases renal tubular calcium re-absorption as well as intestinal calcium absorption. Synthetic PTH (1-34) has been successfully used for the treatment of osteoporosis, where it leads to substantial increases in bone density and a 60-70% reduction in vertebral fractures. 

Bisphosphonates are hrst-line therapy for postmenopausal osteoporosis owing to their established efficacy in preventing hip and vertebral fractures. 

Osteoporosis is a disabling disorder with enormous impact. In addition to the initial pain associated with a new fracture, several adverse long-term complications can occur, including chronic pain, loss of mobility, depression, nursing home placement, and death. Patients with vertebral fractures may experience chronic pain, height loss, kyphosis, and decreased mobility... 

Osteoporosis is the most common skeletal disorder, and approximately one in five Caucasian women in the United States has the disease. The prevalence of vertebral fracture in postmenopausal women is greater than 20%.2 Only one in three patients with osteoporosis has been diagnosed, and only one in seven will receive treatment.2... 

Calcium and vitamin D supplementation increases bone mineral density, and the combination decreases the risk of hip and vertebral fractures. Additionally, vitamin D supplementation decreases nonvertebral fractures in older men and women living independently.11 Because of the effects of calcium on... 

Large, well-designed trials have proven the benefits of bis-phosphonate therapy in preventing vertebral and nonvertebral fractures. Several studies have found decreases in vertebral fracture risk by as much as 40% to 50% with alendronate and risedronate.13,14,19-21 Data suggest a similar reduction with ibandronate on vertebral fractures.16,22 Alendronate and risedronate decrease the incidence of hip and nonvertebral fractures as well.14,19,23... 

Raloxifene increases bone mineral density and reduces fracture rates. In trials of 1 to 3 years, raloxifene increased vertebral and hip bone mineral density by 2% to 3% and 1% to 2%, respectively.30 32 In the Multiple Outcomes for Raloxifene Evaluation (MORE) trial, raloxifene decreased the risk of vertebral fractures by 30% in postmenopausal with at least one prior fracture.30 No significant reduction in nonvertebral fractures was reported. 

Perhaps the most benefit of calcitonin is in patients with or at risk for vertebral fractures. Nasal calcitonin increases vertebral bone mineral density by 1% to 3%.38-40 One 5-year study found a 30% decrease in the risk of vertebral fractures.38 Increases in hip bone mineral density and reductions in non-vertebral fractures have not been demonstrated.38-40 Calcitonin may have analgesic effects in women with back pain from vertebral fractures.41 However, enthusiasm for using calcitonin in this setting has waned in favor of managing fracture risk and pain separately.10... 

Strontium ranelate is an oral agent possessing bone-forming and antiresorptive properties. Some data suggest significant reductions in vertebral fractures.46 However, the benefit in nonvertebral fractures is unclear. This agent has not yet been approved for use by the FDA. 

The most common osteoporosis-related fractures involve the vertebrae, proximal femur, and distal radius (wrist or Colies fracture). Two-thirds of patients with vertebral fractures are asymptomatic the remainder present with moderate to severe back pain that radiates down a leg after a new vertebral fracture. The pain usually subsides significantly after 2 to 4 weeks, but residual, chronic, low-back pain may persist. Multiple vertebral fractures decrease height and sometimes curve the spine (kyphosis or lordosis) with or without significant back pain. 

Raloxifene decreases vertebral fractures and increases spine and hip BMD, but to a lesser extent than bisphosphonates. After discontinuation, the beneficial effect is lost and bone loss returns to age- or disease-related rates. 

Only vertebral fractures have been documented to decrease with intranasal calcitonin therapy. Calcitonin does not consistently affect hip BMD and does not decrease hip fracture risk. 

Calcitonin may provide pain relief to some patients with acute vertebral fractures. If used, it should be prescribed for short-term treatment (4 weeks) and should not be used in place of other more effective and less expensive analgesics, nor should it preclude the use of more appropriate osteoporosis therapy. 

Clinical trials on postmenopausal women with osteoporosis have demonstrated that raloxifene reduces bone turnover markers by 25-35% after 1 year of treatment and reduces the relative risk of the occurrence of new vertebral fractures by 30-50% after 3 years of treatment (Ettinger et al. 1999). A post hoc analysis in women at high risk for cardiovascular diseases also showed a reduction of 40% in the rate of new cardiovascular events (Barrett-Connor et al. 2002), with no observed reduction in the overall study population after 4 years of treatment in the MORE trial. 

Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. Results from a 3-year randomized clinical trial. J Am Med Assoc 282 637-645. Corrections published in J Am Med Assoc 282 2124... 

Vertebral fracture as outcome denotes risk reduction during fourth year of treatment... 

Fig. 8.2. Relationship between change in femoral neck BMD and vertebral fracture risk. MORE trial - 3 years. Similar changes in BMD (dotted line) are related to different fracture risks (arrows) for the raloxifene- and placebo-treated patients. Adapted from (Lufkin et al.

Fig. 8.3. Randomized studies of antiresorptives in postmenopausal women with osteoporosis. Risk of vertebral fractures. Not head-to-head comparison. Increase in lumbar spine BMD vs. placebo (Wright et al. 1994 Liu et al. 2004 Seeman et al. 2003 Ettinger et al. 1998, 1999 Delmas et al. 2002)...

Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC for the FIT trial Research Group (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348 1535-1541... 

Cummings SR, Black DM, Thompson DE, Applegate WB, Barret-Connor E, Musliner TA, Palermo L (1998) Alendronate reduces the risk of vertebral fractures in women witout pre-existing vertebral fractures results of the fracture intervention Trial. J Am Med Assoc 280 2077-2078... 

Delmas PD, Ensrud KE, Adachi JD, Harper KD, Sarkar S, Gennari C, Reginster JY, Pols HAP, Recker RR, Harris ST, Wu W, Genant HK, Black DM, Eastell R for the Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators (2002) Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis four-year results from a randomized clinical trial. J Clin Endocrinol Metab 87 3609-3617... 

Ettinger B, Black D, Cummnings S (1998) Raloxifene reduces the risk of incident vertebral fractures 24 month interim analyses. Osteoporos Int 8(Suppl 3) 11 (abstract)... 

Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut III CH, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD for the VERT Study Group (1999) Effects of risedronate treatment on vertebral and non vertebral fractures in women with postmenopausal osteoporosis a randomised controlled trial. J Am Med Assoc 282 1344-1352... 

Johnell O, Cauley JA, Kulkarni PM, Wong M, Stock JL (2004) Raloxifene reduces risk of vertebral fractures and breast cancer in postmenopausal women regardless of prior hormone therapy. J Fam Pract 53 789-796... 

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