Knochenstoffwechsel, Knochendichte und Östrogenspiegel in der Perimenopause: eine prospektive 2-Jahres-Untersuchung

Zusammenfassung

Der Knochenstoffwechsel und die trabekuläre Knochendichte von 69 prä-, peri- und früh-postmenopausalen Frauen wurden prospektiv untersucht. Marker des Knochenabbaus (BAP = Bonespecific alkalic Phosphatase, knochenspezifische alkalische Phosphatase; OC4 = Osteocalcin) und des Knochenaufbaus (PYD = Pyridinolin, DPD = Desoxypyridnolin, NTX = N-terminales Telopeptid crosslinked Kollagen Typ I, CTX = C-terminales Telopeptid crosslinked Kollagen Typ I) wurden in Serum und Urin zu 5 Zeitpunkten bestimmt (0, 3, 6, 12 und 24 Monaten). Knochendichtemessungen wurden zu Beginn und nach 24 Monaten durchgeführt. Die Ergebnisse der 40 Frauen ohne Hormoneinnahme, die alle Untersuchungen wahrgenommen hatten, wurden bezüglich des Menopausenstatus und der Veränderungen der Messgrößen im Verlauf der 2 Jahre miteinander verglichen. Während die trabekuläre Knochendichte zu Studienbeginn bei den früh postmenopausalen Frauen am niedrigsten war, zeigten die perimenopausalen Frauen den deutlichsten Knochendichteverlust im Studienzeitraum (- 10,6 %). Die Knochenstoffwechselmarker waren in der postmenopausalen Gruppe am höchsten. In der perimenopausalen Gruppe kam es im Verlauf zum Anstieg von OC, PYD und CTX. Perimenopausale Frauen zeigten die höchsten Östrogenwerte.

Abstract

Bone metabolism and trabecular bone density were studied prospectively in 69 pre-, peri- and early postmenopausal women. Markers of bone resorption (OC = osteocalcin, BAP = bonespecific alkalic phosphatase) and bone formation (PYD = pyridinolin, DPD = desoxypyridnolin, NTX = N-terminal telopeptide crosslinked collagen type I, CTX = C-terminal telopeptide crosslinked collagen type I) in serum and urine were followed over a course of two years with five points of examination (0, 3, 6, 12 and 24 months). Bone density was measured at 0 and 24 months. The results of 40 hormonally untreated women who completed all examinations were compared regarding menopausal status and changes over the 2-year-period. While baseline tracecular bone density was lowest in early postmenoapusal women, perimenopausal women showed greatest bone loss (- 10,6 %) during the two year study period. Bone metabolism markers were highest in the postmenopausal group. Perimenopause was associated with a gradual rise in OC, PYD and CTX. Perimenopausal women showed the highest serum estradiol at 0 and 12 months with values exceeding those of premenopausal women. Whether the increased perimenopausal bone loss could be related to the increase in anovulatory cycles during the perimenopausal transition is subject to ongoing investigation.

Perimenopause - Menopause - Knochenstoffwechsel - Knochendichte - Östrogen

perimenopause - menopause - bone density - bone metabolism - estrogen

Literatur

• 1 Bartl R. Osteoporose - Prävention, Diagnostik, Therapie. Thieme Stuttgart, New York 2001
• 2 Blumsohn A, Eastell R. The performance and utility of biochemical bone markers of bone turnover: do we know enough to use them in practice?.  Ann Clin Biochem. 1997;  34 449-459
• 3 Bowman B M, Miller S C. Elevated progesterone during pseudopregnancy may prevent bone loss associated with low estrogen.  J Bone Miner Res. 1996;  11 15-21
• 4 Burger H G, Dudley E C, Robertson D M, Dennerstein L. Hormonal changes in menopausal transition.  Recent Prog Horm Res. 2002;  57 257-275
• 5 Calvo M, Eyre D, Grundberg C. Molecular basis and clinical application of biological markers of bone turnover.  Endocr Rev. 1996;  17 333-359
• 6 Eastell R, Robins S P, Colwell T, Assiri A MA, Riggs B L, Russell R GG. Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption.  Osteoporos Int. 1993;  3 255-260
• 7 Ebeling P R, Atley L M, Guthrie J R, Burger H G, Dennerstein L, Hopper J L, Wark J D. Bone turnover markers and bone density across the menopausal transition.  J Clin Endocrinol Metab. 1996;  81 3366-3371
• 8 Feige A. Klimakterium.  In: Feige A, Rempen A, Würfel W, Jawny J, Caffier H. Frauenheilkunde - Fortpflanzungsmedizin, Geburtsmedizin, Onkologie. 2. Auflage. Urban & Fischer, München, Jena. 2001;  235-274
• 9 Gallagher J C. Role of estrogens in the management of postmenopasual bone loss.  Rheum Dis Clin North Am. 2001;  27 143-162
• 10 Garnero P, Delmas P D. Biochemical markers of bone turnover - applications for osteoporosis.  Endocrinol Metab Clin North Am. 1998;  27 303-323
• 11 Garnero P, Borel O, Delmas P D. Evaluation of a fully automated serum assay for C-terminal cross-linking Telopeptide of type I collagen in osteoporosis.  Clin Chem. 2001;  47 694-702
• 12 Gorai I, Taguchi Y, Chaki O, Nakayama M, Minaguchi H. Specific changes of urinary excretion of cross-linked N-telopeptides of type I collagen in pre- and postmenopausal women: correlation with other markers of bone turnover.  Calcif Tissue Int. 1997;  60 317-322
• 13 Greenspan S L, Parker R A, Ferguson L, Rosen H N, Maitland-Ramsey L, Karpf D B. Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomised clinical trial.  J Bone Miner Res. 1998;  13 1431-1438
• 14 Guthrie J R, Ebeling P R, Hopper J L, Barrett-Connor E, Dennerstein L, Dudley E C, Burger H G, Wark J D. A prospective study of bone loss in menopausal Australian-born women.  Osteoporos Int. 1998;  8 282-290
• 15 Hoshino H, Kushida K, Takahashi M, Yamazaki K, Denda M, Atsumo K, Oikawa M, Toyoyama O, Kawana K, Inoue T. Changes in levels of biochemical markers and ultrasound indices of os calcis across the menopausal transition.  Osteoporos Int. 2000;  11 128-133
• 16 Kawana K, Kushida K, Takahashi T, Ohishi T, Denda M, Yamazaki K, Inoue T. The effect of menopause on biochemical markers and ultrasound densitometry in healthy females.  Calcif Tissue Int. 1994;  55 420-425
• 17 Marcus R, Holloway L, Wells B, Greendale G, James M, Wasilauskas C, Kelaghan J. The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: Results from the postmenopausal estrogen/progestin interventions (PEPI) trial.  J Bone Miner Res. 1999;  14 1583-1595
• 18 Manolagas S C. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis.  End Rev. 2000;  21 115-137
• 19 Prior J C, Vigna Y M, Barr S I, Rexworthy C, Lentle B C. Cyclic medroxyprogesterone treatment increases bone density: a controlled trial in active women with menstrual cycle disturbances.  Am J Med. 1994;  96 521-530
• 20 Prior J C. Perimenopause: the complex endocrinology of the menopausal transition.  Endocr Rev. 1998;  19 397-428
• 21 Randolph J F, Sowers M, Gold E B, Mohr B A, Luborsky J, Santoro N, McConnell D S, Finkelstein J S, Korenman S G, Mathews K A, Sternfeld B, Lasley B L. Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status.  J Clin Endocrinol Metab. 2003;  88 1516-1522
• 22 Ranenevik G, Jeppson S, Johnell O, Bjerre B, Laurell-Borulf Y, Svanberg L. A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density.  Maturitas. 1995;  21 103-113
• 23 Reyes F I, Winter J S, Faiman C. Pituitary-ovarian relationships preceding the menopause I. A cross-sectional study of serum follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol and progesterone levels.  Am J Obstet Gynecol. 1977;  129 557-564
• 24 Riggs B L, Khosla S, Melton L J. Sex steroids and the construction and conservation of the adult skeleton.  Endocrine Rev. 2002;  23 279-302
• 25 Seibel M J, Lang M, Geilenkeuser W J. Interlaboratory variation of biochemical markers of bone turnover.  Clin Chem. 2001;  47 1443-1450
• 26 Seifert-Klauss V, Müller J E, Luppa P, Probst R, Wilker J, Höss C, Treumann T, Kastner C, Ulm K. Bone metabolism during the perimenopausal transition: a prospective study.  Maturitas. 2002;  41 23-33
• 27 The Writing Group for the PEPI trial . Effects of hormone therapy on bone mineral density - results from the postmenopausal estrogen/progestin interventions (PEPI) trial.  JAMA. 1996;  276 1389-1396
• 28 Woitge H W, Seibel M J. Biochemical markers to survey bone turnover.  Rheum Dis Clin North Am. 2001;  27 49-80