Hormone Replacement Therapy in Postmenopausal Women: Urinary N-Telopeptide of Type I Collagen Monitors Therapeutic Effect and Predicts Response of Bone Mineral Density

Chesnut, Charles H.; Bell, Norman H.; Clark, Guy S; Drinkwater, Barbara L.; English, Susan C; Johnston, C. Conrad; Notelovitz, Morris; Rosen, Clifford J.; Cain, Daniel; Flessland, Karen A.; Mallinak, N.

doi:10.1016/s0002-9343(96)00387-7

Cited by 251 publications

(141 citation statements)

References 30 publications

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“…39 Almost half of the patients in the alendronate group in our study had histologically advanced liver disease (stages 3-4); therefore, the measured markers were probably affected by histological stage and did not adequately reflect changes in bone turnover. Furthermore, it is known that NTx levels are lower in postmenopausal women receiving hormone replacement therapy compared with those not receiving hormones, 40 and a large percent of our study patients were on concomitant estrogen therapy.…”

Section: Discussionmentioning

confidence: 91%

Alendronate improves bone mineral density in primary biliary cirrhosis: A randomized placebo-controlled trial

et al. 2005

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Bone loss is a well-recognized complication of primary biliary cirrhosis (PBC). Although it has been suggested that alendronate might improve bone mineral density (BMD) in PBC, no randomized placebo-controlled trial has been conducted. The primary aim of this study was to compare the effects of alendronate versus placebo on BMD and biochemical measurements of bone turnover in patients with PBC-associated bone loss. We conducted a doubleblinded, randomized, placebo-controlled trial. Patients with a PBC and BMD t score of less than ؊1.5 were randomized to receive 70 mg per week of alendronate or placebo over 1 year. BMD of the lumbar spine and proximal femur were measured at entry and at 1 year. Changes from baseline in BMD and biochemical measurements of bone turnover were assessed. Thirty-four patients were enrolled. Seventeen patients were randomized to each arm. After 1 year, a significantly larger improvement (P ‫؍‬ .005) in spine BMD was observed in the alendronate group (0.09 ؎ 0.03 g/cm 2 SD from baseline) compared with the placebo group (؊0.003 ؎ 0.02 g/cm 2 SD from baseline). A larger improvement (P ‫؍‬ .046) was also observed in the femoral BMD of alendronate patients versus placebo. BMD changes were independent of concomitant estrogen therapy. The rate of adverse effects was similar in both groups. In conclusion, in patients with PBC-related bone loss, alendronate significantly improves BMD compared with placebo. Although in this study oral alendronate appears to be well tolerated in patients with PBC, larger studies are needed to formally evaluate safety.

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Section: Discussionmentioning

confidence: 91%

Alendronate improves bone mineral density in primary biliary cirrhosis: A randomized placebo-controlled trial

et al. 2005

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“…These markers have been extensively used for both the assessment of therapeutic efficacy of antiresorptive drugs in osteoporosis and for prediction of fracture risk in postmenopausal women [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. We measured urinary and serum CTx and urinary NTx in a large cohort of untreated, healthy women stratified on the basis of their menopausal status and BMD.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, biochemical markers of bone remodeling are a valuable supplement to bone mineral density measurement (BMD), as they provide a dynamic measure of the current bone turnover state compared with the static measure of skeletal status provided by BMD. Thus, biochemical markers of bone turnover provide a rapid assessment of the effects of antiresorptive therapies such as hormone replacement therapy, bisphosphonates, and calcitonin which induce a decrease in the levels of bone markers that is correlated with the long-term effect of such treatments on bone mass [5][6][7][8][9][10][11][12][13][14][15]. Due to the small annual changes in BMD, the effect of antiresorptive therapy can only be reliably monitored by BMD measurement after several years followup [5,10,13].…”

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confidence: 99%

“…Thus, biochemical markers of bone turnover provide a rapid assessment of the effects of antiresorptive therapies such as hormone replacement therapy, bisphosphonates, and calcitonin which induce a decrease in the levels of bone markers that is correlated with the long-term effect of such treatments on bone mass [5][6][7][8][9][10][11][12][13][14][15]. Due to the small annual changes in BMD, the effect of antiresorptive therapy can only be reliably monitored by BMD measurement after several years followup [5,10,13].Bone markers might also be used to prognose a high rate of bone less in postmenopausal women who would subsequently develop osteoporosis and fractures [16][17][18][19][20][21][22][23][24][25]. Bone turnover increases after menopause and remains elevated in late postmenopausal women.…”

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confidence: 99%

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Bone Resorption in Post-menopausal Women with Normal and Low BMD Assessed with Biochemical Markers Specific for Telopeptide Derived Degradation Products of Collagen Type I

Reginster¹,

Henrotin

Christiansen

et al. 2001

Calcif Tissue Int

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Abstract. Biochemical markers of bone resorption can be used clinically to predict the risk of osteoporosis-related fractures (prognostic tool) and to assess the response of an osteoporotic patient to an antiresorptive therapy (monitoring tool). Our aim was to assess the ability of four currently marketed biochemical markers of bone resorption, based on the measurement of degradation products from collage type I telopeptides to monitor the elevated resorption associated with menopause. Women (846) were stratified for menopause, age, and bone mineral density and the following markers were measured: urinary cross-linked Ntelopeptides of type I collagen (NTx), the levels of breakdown products of type I collagen C-telopeptides in serum (S-CTx), and in urine, by ELISA (U-CTx-E), and RIA (UCTx-R). Furthermore, the ratio (␣/␤) between the ␣L form of CTx measured in the CTx RIA and the ␤L form measured in the ELISA was calculated. The mean difference was calculated for each marker in women with osteopenia (Op) or osteoporosis (PMO) (WHO definition) compared with healthy premenopausal (Pre) women and postmenopausal (N Post) women with normal bone mass. Serum CTx showed the highest elevation in post-compared with premenopausal women. All marker values were significantly higher in Op and PMO subjects compared with both Pre and to N Post women. Compared with premenopausal values, the largest elevation in both Op and PMO women was observed for serum CTx. Compared with N Post, urine NTx showed the highest increase in OP subjects. The ␣/␤ CTx ratio was elevated in post-compared with Pre women, but there was no difference in the ratio among N Post, Op, or PMO women. In conclusion, postmenopausal women showed elevated turnover with all bone resorption markers, but with substantial individual variation in resorption levels. Furthermore, the turnover process in postmenopausal women appears to be quantitatively different from the premenopausal stage, apparent as altered ␣/␤ CTx ratios. Key words: Osteoporosis -Biochemical markers -Bone turnover -Collagen type I -Antiresorptive therapiesDiagnosis.Assessment of bone physiology has been greatly improved by the development of specific and sensitive markers of bone remodeling [1,2]. Biochemical markers have advantages because they are noninvasive, inexpensive, reflect turnover in the whole skeleton, and allow repeated evaluation [3,4]. Furthermore, biochemical markers of bone remodeling are a valuable supplement to bone mineral density measurement (BMD), as they provide a dynamic measure of the current bone turnover state compared with the static measure of skeletal status provided by BMD. Thus, biochemical markers of bone turnover provide a rapid assessment of the effects of antiresorptive therapies such as hormone replacement therapy, bisphosphonates, and calcitonin which induce a decrease in the levels of bone markers that is correlated with the long-term effect of such treatments on bone mass [5][6][7][8][9][10][11][12][13][14][15]. Due to the small annual changes in BMD, the effect...

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“…Thus, these agents may have the additional benefit of preventing increases in BPb levels commonly seen in these life stages. During pregnancy, calcium supplementation is associated with lower BPb levels (22)(23)(24), although calcium given alone has not been proven to reverse the loss of bone mineral density during pregnancy (24) or in postmenopausal subjects (25). In menopausal women, antiresorptive agents such as hormone replacement therapy (HRT) and bisphosphonates are capable of preventing loss of bone density (20,25,26).…”

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confidence: 99%

Skeletal lead release during bone resorption: effect of bisphosphonate treatment in a pilot study.

Gulson

Mizon

Smith

et al. 2002

Environ Health Perspect

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Exposure to lead is still an international public health problem, despite major reductions in its use in industrial processes in developed countries (1). The neurotoxic effects of lead in the fetus, neonate, and infant are well recognized (2). The main reservoir of lead within the body is the skeleton and, until recently, lead was considered to be relatively immobile in this compartment. Recent studies using the stable lead isotope fingerprinting method in nonhuman primates (3,4) as well as in humans (5,6) indicate that lead, like calcium, is mobilized from the maternal skeleton and transferred to the fetus and neonate during pregnancy and lactation. Other times of physiologic stress that could result in additional release of lead from the skeleton include menopause (7). In a preliminary assessment of data from the Third National Health and Nutritional Examination Survey (NHANES III), higher blood lead (BPb) levels were observed in postmenopausal compared with premenopausal women (3.9 vs. 2.6 µg/dL), consistent with the increased bone turnover that occurs during the hormonal changes of menopause. Moreover, higher BPb levels were associated with lower bone density in perimenopausal women (8). Similar relationships in BPb and menopause were noted earlier (9). In a study of 903 women 35-64 years of age from Mexico City, the highest BPb levels were observed in women 47-50 years of age, with a mean difference between pre-and postmenopausal women of 0.76 µg/dL (10). These higher blood levels could have significant health implications because increased BPb levels in adults have been correlated with hypertension (11-16), decreased renal function (17), impaired neurocognitive function (18), and Alzheimer disease (19).Antiresorptive agents that inhibit resorption in the bone remodeling process may reduce or even reverse the demineralization process documented during pregnancy and lactation, observed in perimenopausal women (20), and seen in men and women with corticosteroid-induced osteoporosis (21). Thus, these agents may have the additional benefit of preventing increases in BPb levels commonly seen in these life stages. During pregnancy, calcium supplementation is associated with lower BPb levels (22-24), although calcium given alone has not been proven to reverse the loss of bone mineral density during pregnancy (24) or in postmenopausal subjects (25). In menopausal women, antiresorptive agents such as hormone replacement therapy (HRT) and bisphosphonates are capable of preventing loss of bone density (20,25,26). Postmenopausal women taking HRT have been observed to have significantly higher cortical bone lead concentrations than those not taking HRT (27). To our knowledge there have been no prospective studies to document the effect of antiresorptive agents on BPb levels in healthy adults.We performed a pilot study of the effect of a potent bisphosphonate (alendronate) administered over a 6-month period on BPb levels and other markers of bone turnover in healthy pre-and postmenopausal women and men. The aim of this s...

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Hormone Replacement Therapy in Postmenopausal Women: Urinary N-Telopeptide of Type I Collagen Monitors Therapeutic Effect and Predicts Response of Bone Mineral Density

Cited by 251 publications

References 30 publications

Alendronate improves bone mineral density in primary biliary cirrhosis: A randomized placebo-controlled trial

Alendronate improves bone mineral density in primary biliary cirrhosis: A randomized placebo-controlled trial

Bone Resorption in Post-menopausal Women with Normal and Low BMD Assessed with Biochemical Markers Specific for Telopeptide Derived Degradation Products of Collagen Type I

Skeletal lead release during bone resorption: effect of bisphosphonate treatment in a pilot study.

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