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Osteoporosis


osteoporosis. During this holiday, bone turnover markers and DXA scans should be monitored and drug therapy restarted when bone loss is detected. In patients at high risk of fractures, a one- to two- year drug holiday should be considered after 10 years of treatment. During the drug holiday, high risk patients may benefit from treatment with teriparatide or raloxifene.1


Monitoring Therapy


Osteoporosis is in part defined by low bone mass, as measured by DXA scan. The measurement of BMD also can be used to determine the need for pharmacological therapy; however, once patients are started on pharmacological therapy, the need for follow-up DXA scans is not clearly established. A secondary analysis of data from FIT – a randomised, controlled trial evaluating the fracture benefit of alendronate therapy – was conducted to determine the need for maintenance DXA.22


Patients underwent baseline DXA and yearly


follow-up measurements to monitor the effects of therapy. These serial measurements were made with the same type of machine at all the clinical centers. The secondary analysis used a series of mixed models to determine the benefit of serial DXA scans. The study found a BMD increase of more than 0.019 g/cm2 in 97.5 % of patients taking alendronate, and the authors therefore argue that there is no need for routine monitoring, because BMD increases sufficiently to justify continuing bisphosphonate therapy in all osteoporotic women in the first three years.22


By contrast, in their perspective on the benefits of routine DXA scans during bisphosphonate therapy, Watts and colleagues disagree with the findings of the previous analysis on several key points.23


They


argue that patients whose BMD decreases while on bisphosphonate therapy are at increased risk of fracture, and that it is therefore necessary to identify these patients. They also point out that patients enrolled in large clinical trials are more likely to be compliant with medication than patients in everyday practice, and that patients in clinical trials undergo extensive screening for secondary causes of


1. Watts NB, Bilezikian JP, Camacho PM, et al., AACE Osteoporosis Task Force, American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis, Endocr Pract, 2010;16(Suppl. 3):31–37.


2. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, Osteoporosis prevention, diagnosis, and therapy, JAMA, 2001;265(6):785–95.


3. Jackson RD, LaCroix AZ, Gass M, et al., Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures, N Engl J Med, 2006;354(7):669–83.


4. Chapuy MC, Arlot,ME, Duboeuf F, et al., Vitamin D3 and calcium to prevent hip fractures in the elderly women, N Engl J Med, 1992;327(23):1637–42.


5. Ross AC, Manson JE, Abrams SA, et al., The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know, J Clin Endocrinol Metab 2011;96(1):53–8.


6. Bolland MJ, Avenell A, Baron JA, et al., Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis, BMJ, 2010;341:c3691.


7. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomized controlled trial, BMJ, 2008;336(7638):262–6.


8. Lewis JR, Calver J, Zhu K, et al., Calcium supplementation and risks of atherosclerotic vascular disease in older women: results of 5-year RCT and 4.5-year follow-up, J Bone Miner Res, 2011;26(1):35–41.


osteoporosis that are often missed in clinical practice. (A recent study demonstrated that, in clinical practice, 10 % of patients treated with bisphosphonates lost BMD in the first 1–2 years, which was often due to an unrecognised secondary cause of osteoporosis.)14 Watts et al. also note that the secondary analysis of the alendronate trial was extrapolated to include all bisphosphonates, which is inappropriate.23


In the risedronate trial,24,25 a greater percentage of


patients had reduced BMD after one year than in FIT. Watts and colleague’s final conclusion is that routine DXA screening is not essential to document increased BMD but to identify the subset of patients with declining BMD on therapy in order that the causes of this decline can be identified.23


The AACE recommends baseline and repeat DXA scans every one to two years until findings are stable and then follow-up scans every two years. These scans should be performed at the same facility, using the same machine and, if possible, the same technician, to decrease technical variability. To determine if there has been a change in BMD, the testing facility calculates the least significant change (LSC), which is determined by the facilities’ technologists after performing a precision analysis, and set at 95 % confidence interval for change.1


Conclusion


Osteoporosis is a significant health concern that needs to be appropriately evaluated and treated to prevent morbidity and mortality associated with fractures. Calcium and vitamin D supplementation are the cornerstones of therapy despite recent concerns. Patients should be maintained on 1,200 mg/day of elemental calcium to prevent fractures and sufficient vitamin D to maintain serum 25(OH)D levels at >30 ng/ml. They should be considered for pharmacologic therapy with bisphosphonates or denosumab based on their FRAX score, and for a drug holiday after 5–10 years on treatment. Treatment should be evaluated with routine measurements of BMD to assess bone loss that would require further intervention. n


9. Bolland MJ, Grey A, Avenell A, et al., Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis, BMJ, 2011;342:d2040.


10. Hsia J, Heiss G, Ren H, et al., Women's Health Initiative Investigators, Calcium/vitamin D supplementation and cardiovascular events, Circulation, 2007;115(7):846–54.


11. Melamed ML, Michos ED, Post W, Astor B, 25-hydroxyvitamin D levels and the risk of mortality in the general population, Arch Intern Med, 2008;168(15):1629–37.


12. Vieth R, Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety, Am J Clin Nutr, 1999;69(5):842–56.


13. Heaney R, Holick MF, Why the IOM recommendations for vitamin D are deficient, J Bone Miner Res, 2011;26(3):455–7.


14. Trivedi DP, Doll R, Khaw KT, Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial, BMJ, 2003;326:469.


15. Heaney RP, Functional indices of vitamin D status and ramifications of vitamin D deficiency, Am J Clin Nutr, 2004; 80(6 Suppl.):1706S–9S.


16. Sanders KM, Stuart AL, Williamson EJ, et al., Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial, JAMA, 2010;303(18):1815–22.


17. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al., Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials, BMJ, 2009;339:b3692.


18. Lenart BA, Lorich DG, Lane JM, Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate, N Engl J Med, 2008;358(12):1304–6.


19. Shane E, Burr D, Ebeling PR, et al., American Society for Bone and Mineral Research, Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research, J Bone Miner Res, 2010;25(11):2267–94.


20. Girgis CM, Sher D, Seibel MJ, Atypical femoral fractures and bisphosphonate use, N Engl J Med, 2010;362(19):1848–9.


21. Black DM, Kelly MP, Genant HK, et al., Fracture Intervention Trial Steering Committee, HORIZON Pivotal Fracture Trial Steering Committee, Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur, N Engl J Med, 2010;362(19):1761–71.


22. Bell KJ, Hayen A, Macaskill P, et al., Value of routine monitoring of bone mineral density after starting bisphosphonate treatment: secondary analysis of trial data, BMJ, 2009;338:b2266.


23. Watts NB, Lewiecki EM, Bonnick SL, et al., Clinical value of monitoring BMD in patients treated with bisphosphonates for osteoporosis, J Bone Miner Res, 2009;24(10):1643–6.


24. Bonnick S, Saag KG, Kiel DP, Comparison of weekly treatment of postmenopausal osteoporosis with alendronate versus risedronate over two years, J Clin Endcrinol Metab, 2006;91:2631–7.


25. Bonnick SL, Shulman L, Monitoring osteoporosis therapy: bone mineral density, bone turnover markers, or both? Am J Med, 2006;119(4 Suppl. 1):25S–31S.


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EUROPEAN ENDOCRINOLOGY


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