NEW ASPECTS IN DIAGNOSIS AND TREATMENT OF OSTEOPOROSIS
Abstract
Background. Osteoporosis is a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. In prevention and treatment of osteoporosis, the issue of main interest is prevention of fractures, especially prevention of the first fracture. In recent years, especially after the result of the randomised control trial of Women’s Health Initiative (WHI) was published in the literature, attitudes toward prevention and treatment of osteoporosis have been changed. Hormonal replacement therapy (HRT) use is no longer recommended as a first line treatment, but only a possibility for treatment perimenopausal and early-postmenopausal women with climacteric symptoms and increased risk for fracture, only when therapy benefits outweigh the risks. Today, independent risk factors are taken into account in treatment of osteoporosis, with or without BMD measurement, but including the 10-years risk probability (FRAX – fracture risk assessment tool). There are new possibilites for treatment including a Osteoprotegerin (OPG)/ Receptor Activator of Nuclear factor kappa B (RANK) / Receptor Activator of Nuclear factor kappa B ligand (RANKL) remodelation bone model.
Conclusions. Treatment of osteoporosis is going to be a complex task including all fracture risk factors, polypragmazia which is very common in elderly patents, adherence problems, and last but not least, the economic aspects.
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References
Kocijančič A. Smernice za odkrivanje in zdravljenje osteoporoze.
Zdrav Vestn 2002; 71: 571–3.
Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McDaniel L,
Amin S, Rouleau PA, Khosla S. A population-based assessment
of rates of bone loss at multiple skeletal sites: evidence for substantial
trabecular bone loss in young adult women and men. J
Bone Miner Res 2008; 23:205–14.
U. S. Preventive Services Task Force. Postemnopausal hormone
replacement therapy for primary prevention of chronic conditions:
recommendations and rationale. Ann Intern Med 2002;
: 834–9.
Christiansen C, Christensen MS, McNair P, Hagen C, Stocklund
KE, Transbøl I. Prevention of early postmenopausal bone loss:
controlled 2-year study in 315 normal females. Eur J Clin Invest
; 10: 273–9.
Lindsay R. Prevention and treatment of osteoporosis Lancet
; 341: 801–5.
Kanis J. Pathogenises of osteoporosis and fracture. In: Kanis J.
Osteoporosis London: Blackwell Healthcare Communications;
p. 22–34.
Roux C, Fechtenbaum J, Kolta S, Briot K, Girard M. Mild prevalent
and incident vertebral fractures are risk factors for new fractures
Osteoporos Int 2007; 18: 1617–24.
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg
C, Stefanick ML, et al. Risks and benefits of estrogen plus
progestin in healthy postmenopausal women: principal results
from the Women’s Health Initiative randomized controlled trial.
JAMA 2002; 288: 321–33.
EMEA Public Statement on recent publications regarding hormone
replacement therapy. The European Agency for the
Evaluation of Medicinal Products Post-authoristion Evaluation
of Medicines for Human Use, London, 3 december 2003.
NAMS. Amended report from NAMS Advisory Panel on Postmenopausal
Hormone Therapy. Menopause 2003; 10: 6–12.
Burger H, Archer D, Barlow D, Birkhäuser M, Calaf-Alsina J,
Gambacciani M, et al. Practical recommendations for Hormone
replacement therapy in Peri and Postmenopause. Climacteric
; 7: 210–6.
North American Menopause Society. Estrogen and progestogen
use in peri- and posmenopausal women: March 2007 position
statement of The North Menopasue Society. Menopause 2007;
: 168–82.
Naftolin F, Schneider HP, Sturdee DW; Executive Committee of
the International Menopause Society. Gudelines for the hormone
treatment of women in the menopausal transition and
beyond. Climacteric 2004; 7: 8–11.
Skouby SO. Climacteric Medicine: European Menopause and
Andropause society (EMAS) statements on postmenopausal
hormonal therapy. Maturitas 2004; 48: 19–25.
Šimunić V, Ciglar S, Koršič M, Meden-Vrtovec H, Kocijančič A,
Franić D, et al. Konsenzus II. hrvatsko-slovenskog simpozija o
menopauzi i andropauzi, Plitvice, 8.–10. svibnja 2003. Gynaecol
Perinatol 2003; 12: 133–5.
Utian WH, Archer DF, Bachmann GA, Gallagher C, Grodstein
F, Heiman JR, et al. Estrogen and progestogen use in postmenopausal
women: July 2008 position statement of the North
American Menopause Society. Menopause 2008; 15: 584–602.
Gambacciani M, Cappagli B, Ciaponi M, Pepe A, Vacca F, Genazzani
AR. Ultra low-dose hormone replacement therapy and
bone protection in postmenopausal women. Maturitas 2008;
: 2–6.
Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures
of bone mineral density predict occurence of osteoporotic
fractures. BMJ 1996; 312: 1254–9.
Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix
AZ, et al. Effects of estrogen plus progestin on risk of fracture
and bone mineral density. The Women’s Health Initiative randomized
trial. JAMA 2003; 290: 1729–38.
Siris E, Miller P, Barrett-Connor E, Faulkner KG, Wehren LE,
Abbott TA, et al. Identification and fracture outcomes of undiagnosed
low bone mineral density in postmenopausal women.
Results from the National Osteoporosis Risk assesment JAMA
; 286: 2815–22.
Kanis JA on behalf of the WHO scientific Group. Assessment of
osteoporosis at the primary health-care level. Technical Report.
WHO Collaborting Centre, Univerity of Sheffield, UK; 2008.
Kanis JA on behalf of the WHO Scientific Group. Assessment of
osteoporosis at the primary health care level. WHO Collaborating
Centre for Metabolic Bone Diseases, University of Sheffield;
Kanis JA. Clinical guidelines for the diagnosis and treatment
of osteoporosis. In: 18th IOF Advanced Training Course on
Osteoporosis feb. 3–5, Lyon France; 2009. p. 323–37.
Kanis JA. Treatment of osteoporosis in elderly women. Am J
Med 1995; 98 suppl 2A: 60S–6S.
Comspton JE, Rosen CJ. Pathophysiology. In: Fast facts: Osteoporosis.
Oxford: Health Press; 2009. p. 12–25.
Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms
E, et al. Tumor necrosis factor receptor family member RANK
mediates osteoclast differentiation and activation induced by osteoprotegerin
ligand. Proc Natl Acad Sci USA 1999; 96: 3540–5.
Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy
R, et al. Osteoprotegerin: a novel secreted protein involved in
the regulation of bone density. Cell 1997; 89: 309–19.
Delmas PD. Clinical potential of RANKL inhibition for the management
of postmenopausal osteoporosis and other metabolic
bone diseases. J Clin Densitom 2008; 111: 1221–30.
Glej 34 Kanis JA, Burlet N, Cooper C, Delmas P, Reginster JY,
Borgstrom F, et al. European guidance for the diagnosis and
management of osteoporosis in postmenopausal women. Osteoporosis
Int 2008; 19: 399–428.
Cooper C. Homone replacement therapy. In: 18th IOF Advanced
Training Course on Osteoporosis Lyon France feb. 3–5, 2009. p.
–58.
Genazzani AR, Gambacciani M, Schneider HP, Christiansen C;
International Menopause Society Expert Workshop. Postmenopausal
osteoporosis: therapeutic options. Climacteric 2005; 8:
–109.
Birkhäuser MH, Panay N, Archer DF, Barlow D, Burger H,
Gambacciani M, et al. Updated practical recommendations for
hormone replacement therapy in the peri- and postmenopause.
Climacteric 2008; 11: 108–23.
Kocjan T, Franić D. Osteoporoza in nadomestno hormonsko
zdravljenje. Zdrav Vestn 2008; 77 Suppl 3: III-43–8.
Glej 29. Kanis JA, Burlet N, Cooper C, Delmas P, Reginster JY,
Borgstrom F, et al. European guidance for the diagnosis and
management of osteoporosis in postmenopausal women. Osteoporosis
Int 2008; 19: 399–428.
Delmas PD, McCloskey EV. Clinical use fo selective estrogen
receptor modulators (SERMS) and other estrogen analogs. In:
th IOF Advanced Training Course on Osteoporosis Lyon
France feb. 3–5, 2009. p. 259–64.
Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen
T, Genant HK et al. Reduction of vertebral fracture risk in postmenopausal
women with osteoporosis treated with raloxifene:
results from a 3-year randomized clinical trial. Multiple Outcomes
of Raloxifene Evaluation (MORE) Investigators. JAMA 1999; 282:
–45.
Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE,
Nevitt MC, et al. Randomised trial of effect of alendronate on risk
of fracture in women with existing vertebral fractures. Fracture
Intervention Trial Research Group. Lancet 1996; 348: 1535–41.
Messalli EM, Mainini G, Scaffa C, Cafiero A, Salzillo PL, Ragucci
A et al. Raloxifene therapy interacts with serum osteoprotegerin
in postmenopausal women Maturitas 2007; 56: 38–44
Bartl R, Frusch B. Raloxifen: a potent selective oestrogen receptor
modulator (SERM). In: Bartl R, Frusch B, eds. Osteoporosis diagnosis,
prevention, therapy. Berlin: Springer; 2004. p. 145–7.
Grady D, Ettinger B, Moscarelli E, Plouffe L Jr, Sarkar S, Ciaccia
A, et al. Multiple outcomes of raloxifene evaluation investigators.
Safety and adverse effects associated with raloxifene: multiple
outcomes of raloxifene evaluation. Obstet Gynecol. 2004; 104:
–44.
Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer
M, et al. Effects of raloxifene on cardiovascular events and
breast cancer in postmenopausal women. N Engl J Med 2006;
: 125–37.
DeMichele A, Troxel AB, Berlin JA, Weber AL, Bunin GR, Turzo
E, et al. Impact of raloxifene or tamoxifen use on endometrial
cancer risk: a population-based case-control study. J Clin Oncol
; 26: 4151–9.
Papappoulos SE. Bisphosphonates: Pharmacology and safety.
In: 18th IOF Advanced Training Course on Osteoporosis Lyon
France feb. 3–5, 2009. p. 273–80.
Delmas PD. Clinical use of psphosphonates in postmenopasual
osteoporosis. In: 18th IOF Advanced Training Course on Osteoporosis
Lyon France feb. 3–5, 2009. p. 281–94.
Tonino RP, Meunier PJ, Emkey R, Rodriguez-Portales JA, Menkes
CJ, Wasnich RD, et al. Skeletal benefits of alnedronate: 7-year
treatment of postmenopausal osteoporotic women. Phase III
Osteoporosis Treatment study Group. J Clin Endocrinol Metab
; 85: 3109–15.
Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino
RP, et al. Ten years’ experience with alendronate for osteoporosis
in postmenopausal women. N Engl J Med 2004; 350: 1189–99.
Garnero P, Shih WJ, Gineyts E, Karpf DB, Delmas PD. Comparison
of new biochemical markers of bone turnover in late postmenopausal
osteoporotic women in response to alnedronate
treatment. J Clin Endocrinol Metab 1994; 79: 1693–700.
Odvina CV, Levy S, Rao S, Zerwekh JE, Sudhaker Rao D. Unusual
mid-shaft fractures during long term bisphosphonate therapy.
Clin Endocrinol. V tisku 2009.
Mellström DD, Sörensen OH, Goemaere S, Roux C, Johnson
TD, Chines AA et al. Seven years of treatment with risedronate
in women with postmenopausal osteoporosis. Calcif Tissue Int
; 75: 462–6.
Schnitzer T, Bone HG, Crepaldi G, Adami S, McClung M, Kiel D,
et al. Therapeutic equivalence of alendronate 70 mg once-weekly
and alendronate 10 mg daily in the treatment of soteoporosis.
Alendronate once-Weekly study Group. Aging 2000; 12: 1–12.
Rizzoli R, Greenspan SL, Bone G, Schnitzer TJ, Watts NB, Adami S,
et al. Two-year results of once weekly administation of alndronate
mg for the treatment of postmenopausal osteoporosis. J Bone
Miner Res 2002; 17: 1988–96.
Brown JP, Kendler DL, McClung MR, Emkey RD, Adachi JD,
Bolognese MA, et al. The efficacy and tolerability of risedronate
once a week for the treatment of postmenopausal osteoporosis.
Calcif Tissue Int 2002; 71: 103–10.
Richards JB, Cerkas LF Spector TD: An analysis of which antiosteoporosis
therapeutic regimen would improve compliance
in a population of elderly adults. Curr Med Res Opin 2007; 23:
–9.
Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P. A
review of the literature on osteonecrosis of the jaw in patients
with osteoporosis treated with oral bisphosphonates: prevalence,
risk factors, and clinical characteristics. Clin Ther 2007;
: 1548–58.
Scheper MA, Badros A, Chaisuparat R, Cullen KJ, Meiller TF.
Effect of zoledronic acid on oral fibroblasts and epithelial cells:
A potential mechanism of bisphosphonate-associated osteonecrosis.
Br J Haematol 2009; 144: 667–76.
Atkins GJ, Welldon KJ, Halbout P, Findlay DM. Strontium ranelate
treatment of human primary osteoblasts promotes an osteocytelike
phenotype while eliciting an osteoprotegerin response.
Osteoporos Int 2009; 20: 653–64.
Reginster JY. Anabolic bone agents. In: 18th IOF Advanced
Training Course on Osteoporosis, Lyon France feb. 3–5, 2009.
p. 235–43.
Miller PD, Bolognese MA, Lewiecki EM, Miller PD, Bolognese
MA, Lewiecki, et al. Effect of denosumab on bone density and
turnover in postmenopausal women with low bone mass after
long-term continued, discontinued, and restarting of therapy:
a randomized blinded phase 2 clinical trial. Bone 2008; 43:
–9.
Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, Liu Y,
et al. Effects of denosumab on bone mineral density and bone
turnover in postmenopausal women. J Clin Endocrinol Metab
; 93: 2149–57.
Cummings S, McClung M, Christiansen C, et al. A phase III study
of the effects of denosumab on vertebral, nonvertebral, and hip
fracture in women with osteoporosis: results from the FREEDOM
trial. Presented at the American Society for Bone and Mineral
Research Annual Meeting,, Montreal, QC, Canada, September
, 2008.
Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, et
al. Randomized phase II trial of denosumab in patients with
bone metastases from prostate cancer, breast cancer, or other
neoplasms after intravenous bisphosphonates. J Clin Oncol
; 27: 1564–71.
McCloskey EV. Perspectives in the treatment of osteoporosis.
In: 18th IOF Advanced Training Course on Osteoporosis Lyon
France feb. 3–5, 2009. p. 307–15.
Krishnan G. Lilly commitment in musculo –skeletal research.
In: 8th Regional Forum on Postmenopausal Health Berlin 20–21
October 2007.
Shoback D. Calcimimetics presented at the American Society
for Bone and Mineral Research Annual Meeting, Montreal, QC,
Canada, September 16, 2008.
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