Fast Bone Losers Research Articles

Regional and temporal variation in bone loss during the first year following spinal cord injury.

Osteoporosis is a consequence of spinal cord injury (SCI) that leads to fragility fractures. Visual assessment of bone scans suggests regional variation in bone loss, but this has not been objectively characterised. In addition, substantial inter-individual variation in bone loss following SCI has been reported but it is unclear how to identify fast bone losers. Therefore, to examine regional bone loss, tibial bone parameters were assessed in 13 individuals with SCI (aged 16-76years). Peripheral quantitative computed tomography scans at 4% and 66% tibia length were acquired within 5weeks, 4months and 12months postinjury. Changes in total bone mineral content (BMC), and bone mineral density (BMD) were assessed in ten concentric sectors at the 4% site. Regional changes in BMC and cortical BMD were analysed in thirty-six polar sectors at the 66% site using linear mixed effects models. Relationships between regional and total loss at 4months and 12months timepoints were assessed using Pearson correlation. At the 4% site, total BMC (P=0.001) decreased with time. Relative losses were equal across the sectors (all P>0.1). At the 66% site, BMC and cortical BMD absolute losses were similar (all P>0.3 and P>0.05, respectively) across polar sectors, but relative loss was greatest in the posterior region (all P<0.01). At both sites, total BMC loss at 4months was strongly positively associated with the total loss at 12months (r=0.84 and r=0.82 respectively, both P<0.001). This correlation was stronger than those observed with 4-month BMD loss in several radial and polar sectors (r=0.56-0.77, P<0.05). These results confirm that SCI-induced bone loss varies regionally in the tibial diaphysis. Moreover, bone loss at 4months is a strong predictor of total loss 12months postinjury. More studies on larger populations are required to confirm these findings.

Perimenopausal Bone Loss Is Associated with Ovulatory Activity-Results of the PeKnO Study (Perimenopausal Bone Density and Ovulation).

Background: During the menopausal transition, around 25% of women experience a particularly accelerated loss of bone mineral density. These so-called “fast bone losers” represent a group of patients with an increased risk of osteoporosis. The precise mechanisms underlying this extraordinary level of bone mass reduction have not yet been conclusively elucidated. The PeKnO study (Perimenopausale Knochendichte und Ovulation; Perimenopausal Bone Density and Ovulation) was a 2-year prospective study investigating menstrual cycle changes, hormonal levels, markers of bone metabolism, and changes in bone mineral density (BMD) in perimenopausal women. The PeKnO study specifically focused on the questions of when the maximum of bone loss occurs, whether the decreasing number of ovulatory cycles correlates with increased bone density loss, and which hormones play a role during these processes. Methods: Healthy women aged ≥45 years with menstrual cycles of ≤42 days and without any exogenous hormonal intake continually self-assessed the lengths of their menstrual cycles and the occurrence of LH peaks with the help of a commercially available electronic fertility monitoring device. At baseline and at 6, 12, 18, and 24 months, hormones (LH, FSH, 17β-estradiol, progesterone, cortisol) and markers of bone metabolism (bone-specific alkaline phosphatase (BAP), osteocalcin (OC), and CTX (C-terminal telopeptide) were assessed during the luteal phase. Trabecular bone density was measured in the lumbar spine (vertebrae L1 through L3) by means of quantitative computed tomography (QCT) at the beginning and at the end of the 2-year study period. Patients were divided into 3 groups according to the changes in bone mineral density (BMD) that occurred within the period of 2 years: group I with an increase in BMD, group II with a decrease in BMD of ≤7%, and group III with a decline in BMD of >7%. Women in the latter group were defined as fast bone losers. Results: From a total of 72 recruited patients with an average age of 48.1 (±2.4) at baseline, complete 2-year data were available from 49 participants. Over the course of 24 months, mean bone mineral density decreased by −4.26 (±4.65). In the same time period, the proportion of ovulatory cycles declined from 67% to 33%. The decrease in the ovulatory rate significantly correlated with an enhanced BMD loss (r = 0.68; p < 0.05). Twelve of the forty-nine participants (24.3%) showed a BMD loss of >7% and were identified as fast bone losers. Levels of the luteal phase hormones LH, FSH, 17β-estradiol, and progesterone were significantly different between the three groups. Conclusion: The PeKnO study confirms a marked decline of the ovulatory rate during perimenopause, which is associated with an increased bone density loss while estrogen levels are still adequate.

Predicting patient-specific rates of bone loss at fracture-prone sites after spinal cord injury

Purpose: People with spinal cord injury (SCI) experience bone loss and have an elevated rate of fracture in the paralysed limbs. The literature suggests an exponential time course of bone loss after SCI, but true rates may vary between patients. We propose systematic evaluation of bone status in the early stages of SCI to identify fast bone losers. Method: A case series of six patients with complete SCI were scanned using peripheral quantitative computed tomography within 5 weeks and at 4, 8 and 12 months post-injury. Bone mineral density (BMD) and bone mineral content (BMC) were measured at fracture-prone sites in the tibia and femur. Patient-specific-predictions (PSP) of expected rates of bone loss were produced by individualising published model equations according to each patient’s measured values at baseline. Wilcoxon Signed-Rank tests were used to identify changes between time-points; chi-squared tests for differences between measured and PSP values. Results: In the lower limbs, mean values decreased significantly between baseline and 8 months post-injury, by 19–31% for trabecular BMD, 21–32% for total BMD, and 9–29% for BMC. Most subjects showed no significant differences between PSP and measured values, but individuals with significantly faster rates of bone loss than predicted should be investigated further. Conclusions: There was considerable intersubject variability in rates of bone loss after SCI. Patients showing the fastest bone loss could benefit from continued follow-up and possibly treatment.Implications for RehabilitationSpinal cord injury (SCI) leads to extensive muscle paralysis, and is often accompanied by significant bone loss and increased fracture risk.Repeat bone scans within months of injury can be used to “red-flag” patients who are losing bone faster than predicted.A patient-specific approach to osteoporosis management will facilitate targeted treatment aimed at those who need it most, in SCI and other patient groups.

Cortisol secretion, bone health, and bone loss: a cross-sectional and prospective study in normal nonosteoporotic women in the early postmenopausal period

The aim of the study was to evaluate the relationship between cortisol secretion, bone health, and bone loss in a cohort of normal women in the early postmenopausal period. We measured lumbar and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and heel ultrasound parameters in 82 healthy, nonosteoporotic (lumbar T-score ≥-2.0) women (median age 52.5 years, range 42-61). These women were examined in two sessions, 1 year apart, in the early postmenopausal period (onset of menopause between 6 and 60 months). Parameters of the hypothalamic-pituitary-adrenal (HPA) axis function were morning serum cortisol, morning and midnight salivary cortisol, 24-h urinary free cortisol (UFC), serum cortisol after 0.5 and 1 mg overnight dexamethasone, and DHEA-S. In multiple regression analyses, the following significant inverse correlations were found: i) lumbar BMD and either 24-h UFC (P<0.005) or morning serum cortisol (P<0.05), ii) total femur and femoral neck BMD with morning serum cortisol (P=0.05 and P<0.05), and iii) heel ultrasound stiffness index and midnight salivary cortisol (P<0.005). The annual rate of change in lumbar and femoral BMD did not correlate with any of the above-mentioned hormonal variables. No difference was found in the parameters of HPA axis function in slow (loss of BMD <1%) vs fast (loss of BMD ≥3%) bone losers. HPA axis may contribute to postmenopausal bone health, but differences in cortisol secretion do not influence the differential rate of bone loss between slow and fast bone losers in the early postmenopausal period, at least in healthy women.

Pharmacologic treatment of osteoporosis – 2011

Osteoporosis affects approximately 9% of the population in Hungary resulting in about 100 000 osteoporotic fractures annually. Thirty-five percent of patients with hip fractures due to osteoporosis will die within 1 year. Direct costs of osteoporosis exceed 25 billion forints per year. Apparently, cost-effective reduction of bone loss and consequent fracture risk will add up to not only financial savings but improvement in quality of life, as well. A number of pharmacological modalities are available for this purpose. The mainstay of the treatment of osteoporosis is the bisphosphonate group that includes effective anti-resorptive compounds mitigating bone loss and fragility. The recently registered denosumab exhibits similar efficacy by neutralizing RANK ligand, however, marked differences can be observed between the two drug classes. Strontium has a unique mechanism of action by rebalancing bone turnover, and thus, providing an efficient treatment option for the not fast bone losers who are at high fracture risk. The purely anabolic teriparatide is available for the extremely severe osteoporotic patients and for those who do not respond to other types of therapy. Older treatment options such as hormone replacement therapy, raloxifene, tibolone or calcitonin may also have a restricted place in the management of osteoporosis.

Prediction of bone loss in elderly female subjects by MR perfusion imaging and spectroscopy

To determine whether MR perfusion indices or marrow fat content at baseline can predict areal bone mineral density (BMDa) loss. Repeat dual x-ray absorptiometry (DXA) of the hip was performed in female subjects at 2 years (n = 52) and 4 years (n = 45) following baseline MR perfusion imaging and spectroscopy of the hip. Percentage reduction in femoral neck BMDa at 4 years post-baseline was greater in subjects with below median acetabulum enhancement slope (E(slope)) (-5.6 ± 1.2 Vs -1.1 ± 1.2 (mean ± standard error) p = 0.014) or muscle maximum enhancement (E(max)) (-5.7 ± 1.2 Vs -0.23 ± 1.2, p = 0.009) after adjusting for baseline co-variables. Baseline MR parameters correlated with reduction in BMDa at 4 years (acetabulum E(slope) r = 0.517, p = 0.0003; muscle E(max) r = 0.306, p = 0.043) as well as traditionally applied clinical risk factors. Acetabulum E(slope), femoral neck E(max) and marrow fat content at baseline had sensitivities of 89%, 81% and 72% respectively at distinguishing between fast (>1%/annum) (n = 18) and slow (<1%/annum) (n = 27) BMD losers. Elderly female subjects with reduced perfusion indices at baseline had increased femoral neck bone loss at 4 years. Selected perfusion indices and marrow fat content have a moderate to high sensitivity in discriminating between fast and slow bone losers.

Vitamin D receptor genotype BB is associated with higher serum osteocalcin in first pregnancy

Serum osteocalcin was shown in a previous study on first trimester pregnant women to correlate with bone density and to distinguish between fast and slow bone losers. The objective of the present study is to examine whether serum osteocalcin is related to vitamin D receptor (VDR) BsmI polymorphism in pregnant women. We determined osteocalcin serum levels and VDR BsmI genotype in 97 healthy first trimester pregnant women consecutively recruited during six months. BB (21%), Bb (38%) and bb (41%) genotypes showed similar osteocalcin serum levels. However, in primigravidas (n=38) the BB genotype was significantly associated with higher mean osteocalcin level (9.67 ng/mL) than the Bb (8.07 ng/mL) and the bb genotype (8.14 ng/mL), respectively (P<0.05). The VDR genotype was the only independent parameter to correlate with serum osteocalcin (P<0.05). Only primigravidas show in the first trimester a relation between the bone formation parameter serum osteocalcin and the VDR genotype BB which indicates a higher risk of fractures. For further clinical applications serum osteocalcin and VDR genotype should be tested on a cohort of primigravidas including measurements of bone density.

Changes in bone density and metabolism in pregnancy

The impact of pregnancy on maternal bone density remains unclear. As a prerequisite to investigate the pathophysiology of gestational bone metabolism, we sought to document the changes in bone metabolism biochemistry in conjunction with those in selective trabecular/cortical osteodensitometry between early and late pregnancy. A prospective, controlled study in a university hospital was conducted with 43 healthy women, 34 of them during uneventful pregnancy. The main outcome measures are trabecular and cortical bone density measured in the first and third trimesters using peripheral quantitative computed tomography in conjunction with a panel of bone metabolism parameters, including blood parathyroid hormone, calcitonin, osteocalcin, skeletal alkaline phosphatase, and the urinary desoxypyridinoline/creatinine ratio. Cortical bone density was unaffected by pregnancy. Trabecular bone density changes showed wide interindividual variation, ranging from +1.3 to -20.7% per year, identified as fast losers (less than -3%) and slow losers (more than -3%). Serum osteocalcin levels were lower in slow versus fast bone losers in both trimesters (first: P=0.02, third: P=0.02) and were the only independent parameter to differentiate between fast and slow losers. Our data suggest that wide interindividual variation and the failure to provide a separate measure of trabecular bone density account for the conflicting evidence in earlier reports. Serum osteocalcin concentration during the first trimester distinguishes between fast and slow losers of trabecular bone and should be evaluated in future studies as predictor for later bone loss (osteoporosis).

Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study.

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects ( n=400) were selected by sex and age stratum from the full list of residents born in 1910-1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects ( P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.

Baseline BMD and bone loss at distal radius measured by peripheral quantitative computed tomography in peri- and postmenopausal Hong Kong Chinese women.

The current study was designed to investigate the rate of bone loss in distal radius and its association with baseline volumetric bone mineral density (BMD) and years since menopause (YSM) in peri- and postmenopausal women using precise and multislice peripheral quantitative computed tomography (pQCT; Densiscan 2000). Two hundred and five healthy Hong Kong Chinese perimenopausal ( n = 26) and postmenopausal ( n = 179) women within 10 years of the onset of menopause were recruited. Anthropometric parameters and menstrual status were also measured. The linear regression model derived from the baseline volumetric BMD revealed a significant and slightly better correlation with YSM than age, with a YSM-related annual decline of 2.56%, 1.82% and 0.65% in trabecular BMD (tBMD), integral BMD (iBMD) and cortical BMD (cBMD), respectively. Follow-up measurements after a time interval of 12 months showed that the rate of bone loss was higher than the annual decline in BMD calculated from the baseline BMD, with decreases of 2.89%, 2.16% 0.91% in tBMD, iBMD and cBMD, respectively. Baseline BMD was associated with age or YSM ( r ranges from -0.283 to -0.502; p<0.001 in all cases), but no relationship was found between annual rate of bone loss and age or YSM. The rate of bone loss did not correlate with baseline volumetric BMD values or YSM after dividing the subjects into fast bone losers (with annual tBMD loss > or =3%), normal bone losers (with annual tBMD loss > or = 1% but <3%) or slow bone losers (with annual tBMD loss <1%). The rate of bone loss was greater in both trabecular and cortical bone of postmenopausal women within the first 3 menopausal years but was only significant in the iBMD as compared with perimenopausal and postmenopausal women over 7 years after onset of menopause. The percentage distribution of slow and fast bone losers was not found to be associated with YSM. As a total of only 4 fracture cases were documented, the study could not provide conclusive information on whether perimenopausal and early postmenopausal baseline volumetric BMD or rate of bone loss determines the development of osteoporosis or fracture occurrence.

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.

Clinical Utility of Biochemical Markers of Bone Remodeling

Remodeling is essential for bone health. It begins with resorption of old bone by osteoclasts, followed by the formation of new bone by osteoblasts. Remodeling is coupled (formation is linked to resorption). After middle age or perhaps beginning earlier, bone loss occurs because resorption exceeds formation. This imbalance is accentuated by estrogen deficiency as well as by many diseases and conditions. Biochemical markers that reflect remodeling and can be measured in blood or urine include resorption markers (e.g., collagen cross-links) and formation markers (e.g., alkaline phosphatase). Bone markers exhibit substantial short-term and long-term fluctuations related to time of day, phase of the menstrual cycle, and season of the year, as well as diet, exercise, and anything else that alters bone remodeling. These biological factors, in addition to assay imprecision, produce significant intra- and interindividual variability in markers. Bone marker measurements are noninvasive, inexpensive, and can be repeated often. Unfortunately, most of the studies that provided insight on clinical situations did not focus on markers as a primary endpoint. Bone markers have been useful in clinical practice and have been helpful in understanding the pathogenesis of osteoporosis and the mechanism of action of therapies. In clinical trials, markers aid in selecting optimal dose and in understanding the time course of onset and resolution of treatment effect. Clinical questions that might be answered by bone markers include diagnosing osteoporosis, identifying "fast bone losers" and patients at high risk of fracture, selecting the best treatment for osteoporosis, and providing an early indication of the response to treatment. Additional information is needed to define specific situations and cut points to allow marker results to be used with confidence in making decisions about individual patients.

Fast and slow bone losers. Relevance to the management of osteoporosis.

A low bone mineral density (BMD) is presently regarded as the most important risk factor for the development of osteoporosis. BMD is a function of peak bone mass attained during growth and subsequent age-related bone loss. BMD can be measured accurately and precisely, although the rate of bone loss is more difficult to assess. When axial BMD was measured, the rate of bone loss was shown to increase by 2- to 4-fold at the menopause. Although this rate varies markedly between individuals, it is symmetrically distributed, which argues against the existence of a subpopulation of fast bone losers. Levels of biochemical markers of bone turnover (e.g. osteocalcin, bone specific alkaline phosphatase, deoxypyridinoline) also increase markedly at the menopause, and individuals with a high turnover tend to lose bone more rapidly. Moreover, since increased bone resorption also results in qualitative changes regardless of BMD, a high bone turnover constitutes an independent risk factor. Currently, large intraindividual variations (10 to 40%) in levels of biochemical markers and assay errors still limit our ability to correctly classify individual patients as fast or slow bone losers. The routine use of these markers as a screening tool to predict the risk of osteoporosis in individuals is of limited value, although their selective use in therapeutic decision-making is more promising.

Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture. A 15-year follow-up study

The aim of the study was to examine the role of peak bone mass and rate of postmenopausal bone loss for the subsequent risk of osteoporotic fracture. 182 women within 3 years of menopause were followed longitudinally for 15 years. Over the first 2 years, forearm bone mass (single photon absorptiometry) was measured nine times, the rate of bone loss was calculated, and the women were stratified into a group of bone (n = 49) and a group of bone (n = 133). Later, bone mass was also measured in the lumbar spine and hip with dual energy X-ray absorptiometry. At 15 years, the fast losers had significantly lower body weight (4.4 kG; p < 0.05) than the normal losers. Furthermore, the fast losers had significantly increased values of bone turnover (osteocalcin and C-terminal type I collagen breakdown products). In both the forearm, spine, and hip, the fast bone losers had at all sites significantly less bone mass than the normal bone losers (p < 0.001). 23 women had experienced a peripheral (Colles') fracture and 25 a spinal fracture. The fracture groups had generally significantly (p < 0.05) less bone mass than the group without fracture, both in the forearm, spine, and hip and they also had the highest rate of bone loss after menopause (p < 0.05). Baseline bone mass and rate of loss predisposed to the same extent to fractures with ODD's ratios of about 2. If both low bone mass and rate of loss were present, the ODD's ratio increased to about 3. We conclude that fast rate of bone loss and low bone mass are equally important for the risk of fracture. The identification of women at risk of osteoporosis should therefore consider both a measurement of bone mass status, and a determination of the postmenopausal rate of loss.

Can the fast bone loss in osteoporotic and osteopenic patients be stopped with active vitamin D metabolites?

The aim of this study was to evaluate whether fast trabecular bone loss in osteoporotic and osteopenic patients can effectively be treated with active vitamin D metabolites. Thirty-one osteoporotic and osteopenic patients were monitored between 4 and 22 months before and between 8 and 18 months during the treatment. Fast bone losers were designated as osteoporotic or osteopenic patients with a loss of trabecular bone density in the radius of 3% or more calculated for 1 year. For this differentiation, the high precise peripheral quantitative computed tomography system (DENSISCAN 1000) was used (reproducibility 0.3% in mixed collectives). The pretreatment loss and the "gain" under treatment with active vitamin D metabolites was calculated for 1 year. The treatment consisted of either 0.5 micro;g calcitriol daily or 1 micro;g of alfacalcidol daily. Before treatment, the trabecular bone loss in the radius/year was -6.6 +/- 0.5% (mean +/- SEM). After treatment with vitamin D metabolites, the trabecular bone gain in the radius/year was 0.01 +/- 0.6% (mean +/- SEM). The difference was highly significant (P < 0.001). In contrast to this, the loss of cortical bone density before treatment was -1.8 +/- 0.3% (mean +/- SEM) and the reduced loss after treatment -0.2 +/- 0.4% (mean +/- SEM), both values calculated for 1 year. This difference was less significant (P < 0. 05). This study shows that the treatment with active vitamin D metabolites is very effective in slowing fast trabecular bone loss in osteoporotic and osteopenic patients.

Choice of Reliable Biochemical Markers for Assessment of Bone Remodeling in Postmenopausal Osteoporosis

Objective: To identify those at risk of developing ostoeporosis. Design: Calcium-regulating hormones and markers of bone metabolism (parathyroid hormone mid molecule, parathyroid hormone C-terminal, calcitonin, 1,25 hydroxy vitamin D, total calcium, phosphorus, and cyclic adenosine monophosphate), markers of bone formation [bone alkaline phosphatase (B-ALP), osteocalcin (OC), and carboxyterminal propeptide of type 1 collagen (PICP)], and markers of bone resorption [carboxy-terminal telopeptide of type I collagen (ICTP), pyridinoline, deoxypyridinoline, total hydroxyproline, and N-telopeptide of type I collagen (NTX)] were measured in 36 women with postmenopausal osteoporosis (PMO) with low lumbar spine bone mineral density, 49 healthy premenopausal women, and 30 healthy postmenopausal women with normal lumbar spine bone mineral density. Results: Serum calcitonin and 1,25 hydroxy vitamin D levels of PMO were significantly lower than the corresponding levels of premenopausal women, indicating their clinical value as therapeutic supplements. Among markers of bone formation, OC and B-ALP levels were elevated significantly in women with PMO; there was no significant change in PICP levels in these women when compared with the corresponding levels in controls. Levels of markers of bone resorption—pyridinoline, deoxypyridinoline, and NTX—were significantly elevated in women with PMO, whereas ICTP and total hydroxyproline levels failed to discriminate various groups. Conclusions: B-ALP and OC were equally responsive among formation markers, and NTX and deoxypyridinoline were equally responsive among the resorption markers. These responsive markers are potentially efficient tools for identifying fast bone losers among postmenopausal women. In the present study, bone resorption markers increased over those of bone formation, and the calculated coupling index of their T scores was higher in women with PMO versus healthy postmenopausal women, indicating increased bone resorption in osteoporotic women who had higher rates of bone remodeling than postmenopausal women with normal bone mineral density.

Incidence of fast bone losers and factors affecting changes in bone mineral density: A cohort study in a rural Japanese community

The present study was conducted to determine the incidence of fast bone losers in the general population of a rural Japanese community and factors affecting changes in bone mineral density (BMD). In Miyama village, Wakayama Prefecture, a cohort of 1543 inhabitants aged 40–79 years (716 men and 827 women) was established on the basis of resident registration as of the end of December 1988, and a selfadministered questionnaire survey was performed. Fifty men and 50 women in each of four age strata between 40 and 79 years, totaling 400 participants, were selected randomly. In 1990, an initial examination measuring lumbar BMD by dualenergy X-ray absorptiometry was undertaken on these participants. As a follow-up study, BMD was again measured in the same participants in 1993. Those who showed a decrease in lumbar BMD of at least 3% per year were regarded as fast bone losers, and the incidence of these losers was determined. Factors affecting annual changes in BMD were investigated by multiple regression analysis. The results showed annual changes in 355 (170 men and 185 women) of the participants at the time of the initial examination. The rates of change in BMD in men in their 40s, 50s, 60s, and 70s were −0.53%, −0.40%, −1.07%, and −1.53%, respectively, and those in women in their 40s, 50s, 60s, and 70s were −1.53%, −4.35%, −2.26% and −2.36% in turn. The incidence of fast bone losers was 2.4% (4/170) in men and 9.7% (18/185) in women. As to the results of multiple regression analysis, partial regression coefficients for the rate of change in lumbar BMD were significant for the following items: history of tranquilizer use and Jikei's grading in both sexes; frequency of milk consumption in men; height and body weight at the initial measurement, and frequency of small fish consumption in women. Partial regression coefficients for menopause and the postmenopausal period were also significant in women.

Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study.

The aim of the study was to examine the role of peak bone mass and rate of postmenopausal bone loss for the subsequent risk of osteoporotic fracture. 182 women within 3 years of menopause were followed longitudinally for 15 years. Over the first 2 years, forearm bone mass (single photon absorptiometry) was measured nine times, the rate of bone loss was calculated, and the women were stratified into a group of "fast bone losers" (n = 49) and a group of "normal bone losers" (n = 133). Later, bone mass was also measured in the lumbar spine and hip with dual energy X-ray absorptiometry. At 15 years, the fast losers had significantly lower body weight (4.4 kG; p < 0.05) than the normal losers. Furthermore, the fast losers had significantly increased values of bone turnover (osteocalcin and C-terminal type I collagen breakdown products). In both the forearm, spine, and hip, the fast bone losers had at all sites significantly less bone mass than the normal bone losers (p < 0.001). 23 women had experienced a peripheral (Colles') fracture and 25 a spinal fracture. The fracture groups had generally significantly (p < 0.05) less bone mass than the group without fracture, both in the forearm, spine, and hip and they also had the highest rate of bone loss after menopause (p < 0.05). Baseline bone mass and rate of loss predisposed to the same extent to fractures with ODD's ratios of about 2. If both low bone mass and rate of loss were present, the ODD's ratio increased to about 3. We conclude that fast rate of bone loss and low bone mass are equally important for the risk of fracture. The identification of women at risk of osteoporosis should therefore consider both a measurement of bone mass status, and a determination of the postmenopausal rate of loss.

Prevalence of osteoporosis and prediction of osteoporosis risk in Italian peri- and postmenopausal women: the detection of osteoporosis risk (DOOR) study

The purpose of the Detection of Osteoporosis Risk (DOOR) Study was to determine the incidence of osteoporosis and the distribution of bone turnover levels in a large cohort of Italian peri- and postmenopausal women. We also sought to identify those women at risk of osteoporosis by combining a baseline distal forearm bone mineral content measurement with an estimation of annual percent bone loss as shown by plasma bone Gla protein, serum alkaline phosphatase, and fasting urinary creatinine-corrected calcium and hydroxyproline. A total of 34 centers, distributed uniformly throughout Italy, participated in the study. All women aged 45 to 59 years consulting a select group of primary care physicians for any medical reason were referred to the nearest DOOR center. For 2286 women examined, bone mineral density (BMD) was significantly related to age and years since menopause; 5.0% of the study population had a BMD <2.5 SD of the mean premenopausal reference value and was thus considered to be osteoporotic. Patients were classified as slow (41.7%), borderline (28.2%), and fast (30.1%) bone losers. By integrating the estimated annual percent bone loss with baseline bone mineral content, 27.6% of the postmenopausal women were identified as at risk of developing osteoporosis at age 65 years.

The role of bone loss

Our longitudinal studies of early postmenopausalwomen have shown that there are two characteristic groups. Approximately 35% lose significant amounts of bone mineral (the “fast losers”), whereas approximately 65% lose only a minor amount of bone mineral (the “normal losers”). The rate of bone loss in postmenopausal women may be indirectly assessed by use of a number of biochemical markers. New markers have recently been developed, i.e., more specific and robust markers of both bone resorption and formation. The urinary concentration of degradation products of type I collagen and osteocalcin assays that are stable in serum may optimize the procedure to assess the rate of loss. We and others have shown that these markers correlate to the rate of bone loss with fairly high r values. A prospective 12-year study revealed that the fast bone losers still had significantly higher bone turnover than the normal bone losers. The role of baseline bone mass and rate of loss on fracture risk was evaluated. The data showed that a low baseline bone mass (below -1 SD) and a fast rate of loss predisposed to fracture to the same extent with an odds ratio of approximately 2. A combination of a low baseline bone mass and a fast rate of loss increased the odds ratio of having a fracture. In conclusion, these data suggest that a low bone mass and a fast rate of bone loss play equal roles for the future risk of fracture.