Cortical Bone Resorption in Osteoporosis

A study was made of 110 women: 35 healthy premenopausal, 40 healthy postmenopausal, and 35 women diagnosed as having postmenopausal osteoporosis. The postmenopausal women had similar ages and years since menopause (YSM). In all of the women, total bone mass was evaluated by dual-energy X-ray absorptiometry and metacarpal morphometry was evaluated by radiogrammetry on the second metacarpal of the nondominant hand, performed by computed radiography. An external metacarpal diameter of ≥7.4 mm was required as proof of having developed an adequate peak bone mass. The endosteal diameter, which is indicative of bone resorption in both groups of postmenopausal women, obtained in the postmenopausal groups was subtracted from the endosteal diameter obtained in the premenopausal group and the resulting figure was divided by the years since menopause to calculate the rate of cortical bone resorption/year for each group. The endosteal diameters values differed in the three groups studied (P < 0.0001): 3.2 ± 0.7 mm in the healthy premenopausal women; 3.9 ± 0.6 mm in the healthy postmenopausal women; and 4.7 ± 0.5 mm in the osteoporotic postmenopausal women. The rate of cortical bone resorption was 0.068 ± 0.002 mm/YSM (years since menopause) in the osteoporotic postmenopausal women and 0.033 ± 0.003 mm/YSM in the healthy postmenopausal women (P < 0.0001). These figures reflect the importance of bone resorption, as opposed to deficient bone formation, as a cause of osteoporosis. Received: 27 January 1995 / Accepted: 21 August 1996     

Perimenopausal appendicular bone loss: A 10-year prospective study

The rate of bone loss before and after the menopause were studied prospectively in 73 healthy women, who were all aged 47 and premenopausal at the start of the study. Bone mass was measured annually by radiogrammetry of 6 metacarpals and by dual photon absorptiometry of the distal and proximal forearm. The rate of bone loss was nearly linear the first 6 years both before and after the menopause. At the menopause, the mean rate increased more than 3-fold. The postmenopausal rate of bone loss in the forearm demonstrated an inter-individual normal distribution with a range from 1% to 6% per year. This prospective study suggests that the menopause, and not age per se determines the start of a period with increased rate of bone loss from the appendicular skeleton. As this rate varies considerably between women, estimation of early postmenopausal rate of bone loss will be of importance when advising women concerning prophylactic treatment against osteoporosis.     

Management of cancer treatment-induced bone loss in early breast and prostate cancer - a consensus paper of the Belgian Bone Club

Cancer treatment-induced bone loss (CTIBL) is one of the most important side effects of adjuvant antineoplastic treatment in hormone-dependent neoplasms. Chemotherapy, GnRH analogs and tamoxifen can induce marked bone loss in premenopausal women with early breast cancer. Aromatase inhibitors (AIs) are replacing tamoxifen as the preferred treatment for postmenopausal women. As a class effect, steroidal (exemestane) and non-steroidal (anastrozole and letrozole) AIs increase bone turnover and cause bone loss (4%-5% over 2 years). When compared to tamoxifen, the risk of getting a clinical fracture under AI treatment is increased by 35%-50%. In patients with prostate cancer, androgen deprivation therapy (ADT) increases bone turnover, reduces bone mass (4%-5% per year) and increases the fracture rate depending on the duration of therapy. Zoledronic acid can prevent accelerated bone loss induced by goserelin in premenopausal women, by letrozole in postmenopausal women and by ADT in men. More limited data indicate that weekly alendronate or risedronate could also be effective for preventing CTIBL. Initiation of therapy early, prior to the occurrence of severe osteoporosis, rather than after, may be more effective. Bisphosphonate treatment should be considered in osteoporotic but also in osteopenic patients if other risk factor(s) for fractures are present.     

Skeletal Manifestations of Treatment of Breast Cancer on Premenopausal Women

With increasing use of screening mammography and more effective adjuvant systemic therapies, the majority of women diagnosed with early stage breast cancer will be long-term survivors and experience personal cures. Among the common side effects of adjuvant therapies is treatment-related bone loss, primarily as a result of estrogen deprivation. Whereas this occurs in both postmenopausal and premenopausal women, this brief review will focus on pre- or perimenopausal women when initially diagnosed with breast cancer. An important distinction is between those women who retain ovarian function despite cancer or preventative treatments and the more common situation of premenopausal women who as result of cancer treatments undergo ovarian failure or early menopause. Some women with treatment-related ovarian failure will have sufficient treatment-related bone loss to be at increased risks of subsequent nontraumatic fractures and/or osteoporosis and will be candidates for antiresorptive treatments. The noncancer treatment risk factors, screening and treatments for the management of osteopenia and osteoporosis are generally the same in postmenopausal women with and without breast cancer. However, premenopausal women with relatively rapid onset of treatment-related ovarian failure and bone loss pose several challenges. Awareness of treatment-related bone loss and risks of subsequent osteoporosis is a high priority in an ever-increasing population of breast cancer survivors.     

New approaches to the problems of osteoporosis

Professor Urist's contributions to the understanding of osteoporosis are worthy of reevaluation at this time, when interest in the field has reached unprecedented heights. Recent advances in technology have greatly increased our understanding of osteoporosis by showing that there is no loss of bone in normal premenopausal women, and that the loss which starts at the menopause can be attributed to an increase in bone resorption. It is suggested that the primary event is a rise in plasma calcium that leads to a rise in obligatory urinary calcium loss, which in turn increases the calcium requirement. The subset of the postmenopausal population who develop fractures (particularly in the spine) show additional risk factors, which include malabsorption of calcium (which further increases bone resorption) and reduced adrenal androgen production (which may produce a fall in bone formation). The treatment of established cases requires control of bone resorption by calcium supplementation and/or hormone therapy, with the addition of calcitriol if malabsorption of calcium is present. Stimulation of bone formation is more difficult, but there is a suggestion that this may be possible with the use of anabolic steroids.     

Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women.

The increase in bone fragility after menopause results from reduced periosteal bone formation and increased endocortical resorption. Women with highest remodeling had greatest loss of bone mass and estimated bone strength, whereas those with low remodeling lost less bone and maintained estimated bone strength. INTRODUCTION: Bone loss from the inner (endocortical) surface contributes to bone fragility, whereas deposition of bone on the outer (periosteal) surface is believed to be an adaptive response to maintain resistance to bending. MATERIALS AND METHODS: To test this hypothesis, changes in bone mass and estimated indices of bone geometry and strength of the one-third distal radius, bone turnover markers, and fracture incidence were measured annually in 821 women 30-89 years of age for 7.1 +/- 2.5 years. The analyses were made in 151 premenopausal women, 33 perimenopausal women, 279 postmenopausal women, and 72 postmenopausal women receiving hormone replacement therapy (HRT). RESULTS: In premenopausal women, periosteal apposition increased the radius width, partly offsetting endocortical resorption; therefore, the estimated cortical thickness decreased. Outward displacement of the thinner cortex maintained bone mass and cortical area and increased estimated bending strength. Estimated endocortical resorption accelerated during perimenopause, whereas periosteal apposition decreased. Further cortical thinning occurred, but estimated bending strength was maintained by modest outward cortical displacement. Endocortical resorption accelerated further during the postmenopausal years, whereas periosteal apposition declined further; cortices thinned, but because outward displacement was minimal, estimated cortical area and bending strength now decreased. Women with highest remodeling had the greatest loss of bone mass and strength. Women with low remodeling lost less bone and maintained estimated bone strength. In HRT-treated women, loss of bone strength was partly prevented. These structural indices predicted incident fractures; a 1 SD lower section modulus doubled fracture risk. CONCLUSIONS: Periosteal apposition does not increase after menopause to compensate for bone loss; it decreases. Bone fragility of osteoporosis is a consequence of reduced periosteal bone formation and increased endocortical resorption. Understanding the mechanisms of the age-related decline in periosteal apposition will identify new therapeutic targets. On the basis of our results, it may be speculated that the stimulation of periosteal apposition will increase bone width and improve skeletal strength.     

绝经后骨质疏松与胰岛素样生长因子

目的骨质疏松是老年妇女常见病。绝经后骨丢失主要原因是骨重建单位的骨吸收与骨形成之间平衡失调。胰岛素样生长因子－１（ＩＧＦ－１）是由肝和骨骼合成的生长因子,它参与骨重建,增强成骨细胞活性。方法应用单光子骨密度仪测量非优势前臂桡尺骨中远端１／３交界处桡骨骨密度（ＢＭＤ）,ＢＭＤ低于０．６０１ｇ／ｃｍ２（ｘ－２ｓ）则诊断为骨质疏松。据此将７６名妇女分为绝经前正常妇女（ＮＯＰ１）、绝经后非骨质疏松妇女（ＮＯＰ２）和绝经后骨质疏松妇女（ＯＰ）三组,测定受试者ＩＧＦ－１水平及其他骨代谢指标。结果随着增龄和绝经年限延长,ＩＧＦ－１是维持骨质的重要因子,绝经后妇女增龄,雌激素缺乏,Ｅ２、ＰＴＨ升高可引起血清ＩＧＦ－１水平下降,ＯＰ组低于ＮＯＰ１、ＮＯＰ２组（Ｐ＜０．０５）。所有受试者的ＩＧＦ－１与ＢＭＤ、Ｅ２呈显著正相关（Ｐ＜０．００１）、与年龄（Ａｇｅ）、甲状旁腺激素（ＰＴＨ）呈显著负相关。结论绝经后骨质疏松为高转换率骨质疏松,ＩＧＦ－１水平下降,导致骨吸收超过骨形成,引起骨丢失和骨质疏松。表明ＩＧＦ－１合理用药可以预防骨质疏松     

Expression of Interleukin-6 (IL-6) and IL-6 receptor mRNA in human bone samples from pre- and postmenopausal women.

Interleukin-6 (IL-6) has been attributed to induction of osteoclastogenic-precursor cell proliferation and maturation. Estrogens suppress IL-6 production in stromal/osteoblastic cells in vitro. Conversely, estrogen withdrawal is associated with increased IL-6 production. IL-6 is therefore thought to be an important mediator of the increased bone resorption after menopause. However, evidence supporting a rise in the expression of IL-6 or the IL-6 receptor in human bone tissue with menopause is still lacking. To address this question, we established a 5'-nuclease assay to quantitate the expression of human IL-6 and the gp80 subunit of the IL-6 receptor in human bone samples. The number of mRNA copies was normalized to the number of copies of beta actin mRNA. Osteocalcin expression served as an independent control. The study population consisted of 169 women (mean age 52.4 +/- 11.6 years) who underwent surgery for early breast cancer. Serum IL-6 was measured by enzyme-linked immunosorbent assay, serum crosslaps as a marker of bone resorption were measured by electrochemiluminescent assay, and serum osteocalcin was measured by chemoluminescence assays. RNA expression of osteocalcin in bone tissue from early postmenopausal women was higher compared with premenopausal women. Local expression was positively associated with circulating osteocalcin and crosslaps concentrations. Postmenopausal women also had higher circulating IL-6 concentrations. In contrast, bone samples from postmenopausal women lacked an increased expression of either IL-6 or gp80 compared with bone samples from premenopausal women. In conclusion, we failed to detect local increases in IL-6 or IL-6 receptor expression in human bone tissue with menopause. If direct changes in the IL-6 system in bone tissue are involved in postmenopausal bone loss, these changes appear to be below the detection limit of our assay system.     

Reduction in normalized bone elasticity following long-term bisphosphonate treatment as measured by ultrasound critical angle reflectometry

Using an improved version of ultrasound critical angle reflectometry, the bone quality of cortical and trabecular bone was assessed in vivo by measuring elastic moduli (normalized for bone density) at both principal axes, referred to as the minimum and maximum normalized elasticities. The measurements were made in 30 normal premenopausal women, 30 normal postmenopausal women, 22 untreated postmenopausal women with osteoporosis, 74 postmenopausal women with osteoporosis or osteopenia on bisphosphonate treatment, and 32 patients with renal transplantation (16 women and 16 men) taking steroids. Cortical elasticity was higher than trabecular elasticity; both declined slightly and non-significantly with age in normal women. Among untreated postmenopausal women with osteoporosis, cortical maximum normalized elasticity (E_cmax) remained within 95% prediction intervals of normal women. Among patients on bisphosphonate, E_cmax was low in the majority of patients. E_cmax was significantly more depressed among those taking the drug 3 years than <3 years (22.1% below normal premenopausal women versus 17.2%, P =0.001), and among those with incident non-spinal fractures than without (75.9 vs. 81.5%, P =0.008). E_cmax was independent of bone mineral density at the calcaneus. Most patients with renal transplantation had low E_cmax, with a mean 20.8% below the normal premenopausal mean. Qualitatively similar findings were found with cortical minimum elasticity and with trabecular minimum and maximum elasticities. Thus, the material bone quality of cortical and trabecular bone may be impaired following bisphosphonate treatment, as in renal transplantation on steroids.     

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

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

Dental panoramic radiograph as a tool to detect postmenopausal women with low bone mineral density: untrained general dental practitioners' diagnostic performance

The detection of postmenopausal women with low bone mineral density (BMD) is an important strategy to reduce the incidence of osteoporotic fracture. Recent studies suggested that incidental findings on dental panoramic radiographs may be used as a tool to detect women with low BMD. However, little is known whether this finding is sufficiently assessed by untrained general dental practitioners (GDPs). The purpose of this study was to investigate: (1) the observer agreement and (2) the diagnostic efficacy in detecting women with low BMD, when untrained GDPs assess the appearance (normal or eroded) of the mandibular inferior cortex on dental panoramic radiographs of postmenopausal women. Twenty-seven GDPs were asked to classify the appearance of the mandibular inferior cortex on dental panoramic radiographs of 100 postmenopausal women who had completed BMD assessments of the lumbar spine and of the femoral neck. Intra-and inter-observer agreements were analyzed with kappa statistics. The diagnostic efficacy (sensitivity, specificity and predictive values) was analyzed by comparing two groups classified by the mandibular inferior cortex (women with normal and women with eroded mandibular inferior cortex) with those classified by BMD (women with normal BMD and women with osteopenia or osteoporosis). The mean sensitivity and specificity were 77% and 40%, respectively, when BMD of the lumbar spine was used as standard and 75% and 39%, respectively, when BMD of the femoral neck comprised the standard. Nineteen untrained GDPs (70%) presented a moderate to almost perfect intra-observer agreement. We conclude that dental panoramic radiograph may be used in clinical dental practice to identify postmenopausal women who have undetected low BMD and should undergo further testing with bone densitometry.     

绝经前后妇女骨代谢生化指标与骨超声声速的关系

目的 观察绝经前后不同年龄妇女的骨超声声速和骨代谢生化指标的变化情况及相互关系。方法 共197例绝经前后妇女,其中89例为绝经前组,接年龄每隔10年分组,88例为绝经后组。用ELISA法测定各个骨形成与骨吸收指标,同时B超亩骨密度仪测定骨超声声速情况。结果 绝经前骨超声声速无明显改变,绝经后骨超声声速明显下降,骨超声声速在绝经后与年龄及绝经年限呈负相关。骨超声声速与骨吸收指标呈负相关。骨吸收指标Pyd不但在绝经后明显上升,且在绝经前的第3组妇女中已较前有明显升高。结论 骨代谢生化指标的改变先于骨超声声速的改变,骨量和骨代谢指标测定相结合,可能更有助于预测将来发生骨折的危险程度。     

Evidence that type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency

Type I osteoporosis occurs within 20 years after menopause and is associated with excessive cancellous bone loss and fractures of the vertebrae and distal radius. We have suggested that it may be caused by estrogen deficiency plus some additional factor predisposing to excessive bone loss. One such factor might be a greater degree of sex steroid deficiency, a possibility that could not be previously excluded because assays of sufficient sensitivity have only recently become available. Thus, we studied 36 women with vertebral fractures due to typical high turnover type I postmenopausal osteoporosis and 36 normal postmenopausal women using new ultrasensitive assays with detection limits of 1 pg/ml for estradiol, 5 pg/ml for estrone and 5 ng/dl for testosterone to test if type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency. Mean levels of serum sex steroids were identical in both groups, but bone turnover was increased by up to 55% in the women with type I osteoporosis. Moreover, compared with controls, the osteoporotic women had a 51% higher (P<0.01) serum osteoprotegerin level, which was likely a compensatory response to the increased bone turnover. In the osteoporotic women, 1-year treatment with transdermal estrogen in 14 women reduced total deoxypyridinoline, an index of bone resorption, by 58% as compared with placebo treatment in 17 women (P<0.001). Thus, as compared to controls, postmenopausal osteoporotic women had comparable sex steroid levels but higher bone turnover levels that were responsive to estrogen therapy. This is consistent with the hypothesis that the greater bone loss in type I osteoporosis is the result of impaired responsiveness of bone to low postmenopausal levels of sex steroids.     

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

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 N-telopeptides 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 (U-CTx-R). Furthermore, the ratio (alpha/beta) between the alphaL form of CTx measured in the CTx RIA and the betaL 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 alpha/beta 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 alpha/beta CTx ratios.     

Serum tartrate-resistant acid phosphatase and bone mineral content in postmenopausal osteoporosis

Summary Serum tartrate-resistant acid phosphatase (sTr-AcP) and bone mineral content (BMC) were measured in 29 women with postmenopausal osteoporosis and in 12 control women. Serum Tr-AcP was higher in osteoporotic patients than in controls and a negative linear correlation was found between sTr-AcP and BMC in osteoporotic women. These results suggest that sTr-AcP could be a useful marker for bone loss and consequently, for the measure of bone resorption rate in postmenopausal women.     

Alteration of the circadian rhythm of intact parathyroid hormone and serum phosphate in women with established postmenopausal osteoporosis

Several studies have established that the circulating concentration of intact parathyroid hormone, PTH (1–84), over 24 h follows a circadian rhythm. The importance of this circadian rhythm is not known although some authors have detected alterations in the rhythm in metabolic bone disease and following dietary manipulation. We have studied the circadian rhythm of PTH (1–84) in 8 premenopausal women, 8 postmenopausal women with established osteoporosis and 8 postmenopausal women with no evidence of osteoporosis. Blood samples were obtained at 30-min intervals over a 24-h period and significant differences were found in the profiles of PTH (1–84) and serum phosphate in the three groups studied. Premenopausal women possessed a nocturnal/early morning increase in PTH (1–84) and phosphate (between 2200 and 0700 hours), as did postmenopausal women without osteoporosis. In postmenopausal women with osteoporosis the nocturnal increase in PTH (1–84) and serum phosphate was absent and PTH (1–84) decreased during the period 2200-0700 hours. A shift in acrophase is observed between premenopausal and postmenopausal women without osteoporosis. No acrophase was found in postmenopausal women with osteoporosis for either PTH (1–84) or serum phosphate. No circadian rhythm, acrophase or significant amplitude was observed in serum adjusted calcium or ionized calcium in any group studied. Alterations in the circadian rhythms for PTH (1–84) and serum phosphate occur in patients with postmenopausal osteoporosis that suggest the normal dynamics of PTH (1–84) secretion may play a role in both calcium and phosphate metabolism and the bone remodelling process. Whether these changes are causative or a response to the pathology will require further investigation.     

绝经后骨质疏松症发病机制研究进展

绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)是指女性绝经后卵巢内分泌功能失调衰退,导致雌激素水平下降,从而导致破骨细胞的骨吸收大于成骨细胞的骨形成的一种代谢性疾病。骨质疏松症没有特异性的临床表现,直到轻微的创伤诱发骨折时才会引起重视,所以预防骨质疏松症是临床工作的重中之重。目前有很多研究报道了骨质疏松症发生发展的机制,在机体内雌激素的缺乏引起炎症因子与MicroRNA激活,从而引起RANKL-RANK-OPG轴的紊乱,引起骨质流失。同时雌激素充当抗氧化剂来保护骨,抵抗氧化应激。本文就绝经后骨质疏松症的发生机制做一综述。     

Prognostic interest of bone turnover markers in the management of postmenopausal osteoporosis

ObjectiveThe aim was to review the literature dealing with the use of biochemical bone turnover markers (BTM) as predictors of bone loss and individual risk of fracture in postmenopausal osteoporosis.MethodsWe performed a generalized search in MEDLINE using Mesh Database from 1995 through 2009 with the following terms “biological markers” with “osteoporosis” or “bone resorption”, or “bone fracture”, “fracture risk”. From this research, 197 abstracts were read, 91 articles were screened then 43 original articles were selected.ResultsIn most of the selected articles, the upper limit of the premenopausal range was used as a cut-off definition for increased bone resorption. Based on this review, we found a moderate and positive relationship between baseline level of BTM and rate of bone loss, more particularly for high level of BTM over 2 SD, especially when high turnover is constant in repeated sampling. In addition, an increase in BTM levels is associated with an increase in the risk of hip and non-vertebral fractures in elderly women over 75 years old. This is especially demonstrated with bone resorption markers (e.g. uCTX) in the highest quartile with an 1.7 to 2.2 fold increase. The combination of data from bone mineral density (BMD) and bone resorption markers may improve fracture prediction.ConclusionThe measurement of BTM, together with the assessment of other risk factors including low BMD, will improve the prediction of risk facture, but there is a lack of practical guidelines.     

Metacarpal Radiogrammetry by Computed Radiography in Postmenopausal Women with Colles' Fracture and Vertebral Crush Fracture Syndrome

Based on the hypothesis that the underlying osteoporotic mechanism of Colles' fracture in postmenopausal women is similar to that of other osteoporotic fractures, that is, cortical bone resorption as opposed to cancellous bone resorption, the rate of corticoendosteal bone loss was compared in 40 normal postmenopausal women [average age 68.4 ± 7.1 years; 20 ± 4 years since menopause (YSM)], in 35 postmenopausal women with Colles' fracture (age 69.4 ± 7.5 years, 22 ± 8 YSM), in 35 normal postmenopausal women with vertebral crush fracture (age 69.4 ± 7.5 years, 22 ± 8 YSM, and in 35 normal premenopausal women (age 36.1 ± 7.9 years). Radiogrammetry by digital radiography of the second metacarpal was used to measure external (ED) and internal (ID) diameter, cortical thickness (CCT), cortical area (CA), and the ratio of cortical area to total area (CA/TA). The ID values of the groups of postmenopausal women were subtracted from the ID value of the premenopausal women and the result was divided by YSM to obtain the rate of corticoendosteal resorption/year (ΔC), CA resorption year (ΔCA) and CA/TA resorption/year (ΔCA/TA). ID, ΔC, ΔCA, and ΔCA/TA all were larger in the postmenopausal women with Colles' and vertebral crush fractures than in the normal postmenopausal women (ANOVA: all P < 0.0001). ID, CCT, ΔC, CA, ΔCA, and ΔCA/TA did not differ between the two groups of postmenopausal women with fractures. ΔC was 87% greater in postmenopausal women with vertebral crush fracture and 116% greater in women with Colles' fracture than in normal postmenopausal women. These results indicate that the loss of cortical bone is an important factor in Colles' fracture in postmenopausal women. Received: 10 October 1996 / Accepted: 15 October 1997     

Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study.

The ability of biochemical markers to predict the rate of postmenopausal bone loss is still controversial. To investigate this issue further, baseline levels of a panel of specific and sensitive biochemical bone markers were correlated to the rate of change of forearm bone mineral density (BMD) assessed by four measurements over a 4-year period using dual-energy X-ray absorptiometry in a large population-based prospective cohort of 305 women aged 50-88 years (mean 64 years), 1-38 years postmenopausal. In the whole population, higher baseline levels of bone formation (serum osteocalcin and serum type I collagen N-terminal propeptide) and bone resorption markers (urinary N-telopeptides; urinary and serum C-telopeptides) were significantly associated with faster BMD loss (r = -0.19 to -0.30, p < 0.001), independently of age. In women within 5 years of menopause that have the highest rate of bone loss, the predictive value of bone markers was increased with correlation coefficients reaching 0.53. Women with an abnormally high bone turnover, i.e., with levels of bone markers at baseline 2 SD above the mean of premenopausal women, had a rate of bone loss that was 2- to 6-fold higher than women with a low turnover (p = 0.01-0.0001) according to the marker. When the population was categorized according to quartiles of bone markers at baseline, a similar relationship between increased levels of bone markers and faster rate of bone loss was found (p = 0.008-0.0001). In the logistic regression model, the odds-ratio of fast bone loss, defined as the rate of bone loss in the upper tertile of the population, was increased by 1.8- to 3.2-fold for levels of biochemical markers in the high turnover group compared with levels within the premenopausal range, with, however, a limited value for identifying individual fast bone losers. We conclude that increased levels of some of the new biochemical markers of bone turnover are associated with greater radial bone loss. Because increased bone loss is associated with an increased risk of fracture, bone turnover markers may be useful to improve the prediction of the risk of osteoporosis in postmenopausal women.