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PubMed1991

Bone mineral density and anorexia nervosa in women.

OBJECTIVE: A review of reports of reduced bone mineral density in women with anorexia nervosa was undertaken in order to profile specific risk factors, which could then be used as the basis for suggestions for future research and treatment. METHOD: Thirteen research studies and four case studies of reduced bone mineral density and fractures in women with anorexia nervosa were reviewed. The relationships between bone mineral density and amenorrhea, estrogen, calcium intake, physical activity, parathyroid hormone, alkaline phosphatase, 1,25-dihydroxyvitamin D, cortisol, and growth hormone were examined in the reports of these studies and other reports of altered physiology during anorexia nervosa. RESULTS: The average spinal, radial, and femoral bone mineral density in anorexic women was significantly lower than it was in normal control subjects. Concurrent with the low intake of nutrients by individuals with anorexia nervosa, low body weight, early onset and long duration of amenorrhea, low calcium intake, reduced physical activity, and hypercortisolism appeared more likely to contribute to decreased bone mineral density than did other abnormal aspects of the disorder. CONCLUSIONS: Future research needs to address how such factors as amenorrhea and hypercortisolism affect bone mineral density in anorexia nervosa. Since no controlled trials of estrogen replacement or calcium supplementation in anorexia nervosa have been reported, the proper treatment for decreased bone mineral density is not known. However, the most obviously important intervention is to encourage medical stabilization and weight gain.

Adolescent↗
PubMed1999

Blood circulation as source for osteopontin in acellular extrinsic fiber cementum and other mineralizing tissues.

Osteopontin (OPN) is one of the major non-collagenous proteins in root cementum and other mineralized tissues. Although most of this mineral-seeking protein is thought to be produced by local tissue cells, some of it might enter the mineralizing matrix from the blood. To test this hypothesis, we followed the distribution of a single dose of purified porcine or rat 125I-labeled OPN injected i.v. in rats, in mineralizing and non-mineralizing tissues and in subcutaneously implanted collagenous implants. The animals were killed 30 or 48 hrs after injection. Tissues (calvaria, tibia, lower and upper jaws) were harvested and processed for radioautography and biochemical analysis. Tissues as well as calcifying collagenous implants proved to have taken up radiolabel. In EDTA extracts of long bones, the majority of the radiolabel was demonstrated to be associated with intact OPN. The iodinated protein was also found in the acellular extrinsic fiber cementum (acellular cementum) layer investing the continuously growing incisors, in laminae limitantes, cement lines, and in forming bone near the mineralization front. Further, the label was present in the circumpulpal dentin of the incisors, and some of it appeared to have been incorporated into developing enamel. It is concluded that OPN in acellular cementum and other mineralizing tissues may-at least partially-originate from sources outside the direct environment following its transportation via serum.

Animals↗
PubMed1989

Enamel hypomineralization viewed from the pattern of progressive mineralization of human and monkey developing enamel.

Microradiograms and their computer-aided image analysis of ground sections of the developing enamel of human permanent third molars and monkey permanent teeth (Macaca fuscata) indicate that the mode of progressive mineralization of enamel is completely different between the matrix formation and maturation stages. During the former stage, the enamel matrix is slightly mineralized. During the latter stage, which takes a much longer period than the previous stage, the increase in the secondary mineralization takes place first slightly, from the surface toward the inner layer, and then heavily, from the inner layer toward the surface. The narrow outer layer mineralizes very slowly during the middle and late stages of maturation, but finally achieves the highest mineralization of the entire enamel layer. The very narrow innermost layer mineralizes slowly without expanding its width. The former three processes seem to be under the direct control of the ameloblasts. Hypoplastic areas which appear during the matrix formation stages are not necessarily accompanied by hypomineralization. Dysfunction of the cells immediately after the completion of matrix formation appears to cause hypomineralization throughout the entire width of matrix except for the innermost layer. Disorders of the cells occurring during the middle and/or the late stage of maturation--due to chronic metabolic disturbances, such as fluorosis--induced hypomineralization localized mainly at the outer layer. The hypomineralized enamel is not necessarily accompanied by hypoplasia. The process of enamel mineralization is not necessarily fully synchronized with that of tooth eruption. Therefore, the narrow outer layer, especially in the fissure and cervical regions, is sometimes hypomineralized even after the teeth have erupted normally.

Animals↗
PubMed1994

A portable dual energy x-ray absorptiometry technique for the measurement of bone mineral in preterm infants.

A dual energy x-ray absorptiometry technique has been developed for the measurement of bone mineral in preterm infants. Two films are taken of the infant's forearm using a standard mobile x-ray set on the ward at two x-ray energies. Included in the field of view is a double step wedge made of aluminum and Perspex. The images are digitized by viewing them on a light box with a TV camera. The bone mineral content in the forearm can then be mapped by the measurement of light intensity in matching pixels of the two films and comparison with the intensities in the step wedge. The bone mineral concentration in the radius, expressed as bone mineral per unit length (mg/mm), is calculated. The technique has been tested using phantoms of calcium hydroxylapatite set in a tissue equivalent material and in Perspex. It has been shown that the reproducibility of the technique is approximately 7% and that there is a systematic underestimate of bone mineral of about 17%. The technique has been shown to be linear up to a bone mineral concentration of 8 mg.mm-1. Longitudinal studies for 14 infants that show an initial 6-wk period of demineralization after birth with a subsequent mineralization phase are reported.

Absorptiometry, Photon↗
PubMed1990

Comparative study of the changes in insulin-like growth factor-I, procollagen-III N-terminal extension peptide, bone Gla-protein, and bone mineral content in children with Turner's syndrome treated with recombinant growth hormone.

Six girls (7-13 yr old) with Turner's syndrome and short stature were treated for 1 yr with recombinant human GH (0.15 U/kg.day, sc) and had sequential determinations of serum insulin-like growth factor-I (IGF-I), osteocalcin, and procollagen-III. Bone mineral content and density of the spine and radius were measured before treatment and at 90 and 360 days. Two girls received small doses of ethinyl estradiol (0.025 micrograms/kg) in addition to GH. Height velocity increased by 144% after 3 months of treatment. IGF-I was normal (0.75 +/- 0.20 kU/L) before treatment and increased by 90% on day 1 and by 290% on day 360. Procollagen-III was low before treatment; it peaked at 53.0 +/- 14.7 micrograms/L (260% above baseline) on day 30, then decreased to the normal range. Serum osteocalcin increased more slowly to reach a plateau on day 90 of 23.7 +/- 1.2 micrograms/L (46% above baseline). Before treatment, bone mineral content of the spine was 25% lower than that of children matched for bone age. Bone mineral contents of the peripheral and axial skeleton were increased by 10% and 17%, respectively, after 1 yr of treatment, an increase commensurate with that of bone age in the four patients who did not receive estrogen. On day 90, however, although radius mineral density was already increased by 3%, the mineral density of the lumbar spine was significantly decreased by 4%. We conclude that treatment with GH increases IGF-I, collagen turnover, osteoblastic function, and height velocity in Turner's syndrome. However, there is no catch-up of bone mineral content after 1 yr of treatment, and an early effect of GH is to decrease spine mineral density.

Adolescent↗
PubMed1996

A longitudinal evaluation of bone mineral density in adult men with histories of delayed puberty.

We have previously demonstrated that men with histories of constitutionally delayed puberty have significantly lower spinal and radial bone mineral density than normal men. Because these men were in their mid-twenties, it is possible that bone density was decreased because bone development was still incomplete. In addition, there is no information on the bone density of the proximal femur, the most important clinical site for osteoporotic fractures, in men with histories of delayed puberty. To address these issues, we performed repeat measurements of radial and spinal bone mineral density 2 yr after the initial evaluations in 18 men with histories of delayed puberty. Bone mineral density of the femoral neck was also measured at the time of follow-up evaluations. The mean radial bone mineral density at the time of the repeat evaluations was similar to the mean value from the initial evaluations (0.74 +/- 0.08 vs. 0.74 +/- 0.07 g/em2) and the mean change was 0.00 +/- 0.04 g/cm2. Similarly, the mean spinal bone mineral density at the time of the repeat evaluations was similar to the mean value from the initial evaluations (1.02 +/- 0.10 vs. 1.01 +/- 0.10 g/cm2) and the mean change was -0.01 +/- 0.04 g/cm2. Bone mineral density of the femoral neck was significantly lower in the men with histories of delayed puberty than in normal men (0.88 +/- 0.11 vs. 0.98 +/- 0.14 g/cm2 P < 0.02). These data indicate that bone accretion is complete by the mid-twenties in men with histories of constitutionally delayed puberty and that their bone mineral density does not improve with time. In addition, these men have decreased bone density of the femoral neck, which might increase their risk for hip fractures when they are older.

Adult↗
PubMed1998

Familial resemblance for bone mineral mass is expressed before puberty.

Genetic factors are known to explain a major proportion of peak bone mineral mass variance. Whether the influence of these genetic factors is expressed before the pubertal bone mineral mass accrual and whether there is tracking of bone mineral mass during pubertal growth, however, are not clearly established. We prospectively investigated correlations for bone mineral content (BMC), density, and bone size between prepubertal daughters and their premenopausal mothers. Height, weight, lumbar spine (LS), femoral neck (FN) and mid-femoral diaphysis BMC, bone area (BA), areal bone mineral density (aBMD), and volumetric bone mineral apparent density (BMAD) were evaluated in 138 mothers (mean age +/- SD, 40.0 +/- 4.0 yr) and their daughters (8.1 +/- 0.7 yr), who were then remeasured at yearly intervals for 2 yr. Eight-year-old prepubertal daughters had reached 78% and 44% of their mothers' height and weight, respectively. At the various skeletal sites, they had reached 33-43% of their mothers' BMC, 47-69% of their BA, 59-78% of their aBMD, and 75-105% of their BMAD. All body size and bone traits (age-adjusted Z-scores) were significantly correlated between prepubertal daughters and their mothers (r: 0.22-0.36, P < 0.01), except midfemoral diaphysis BMAD. Heritability estimates (1/2 h2), after adjustment for body size and dietary calcium intake, showed that 18-37% of bone traits were directly determined by maternal descent. During the next 2 yr, growth was accompanied by a marked increase of BMC, aBMD, and BA, whereas BMAD changed very little. In contrast, during this period, there were only minor changes in body size or bone trait Z-scores (i.e. < 0.5 Z-scores), which were thus highly correlated between consecutive measurements (r: 0.75-0.92, P < 0.0001). Accordingly, mother-daughter correlations remained unchanged over that period. Although more than 60% of peak bone mineral mass is gained during puberty (mostly at the expense of an increase in bone size while volumetric bone density slightly changes), familial resemblance for most bone traits is already present between daughters and their mothers before puberty. In the girls, moreover, yearly measurements were highly correlated, suggesting tracking of bone traits during pubertal growth. These results indicate that genetic susceptibility to osteoporosis may already be detectable in early childhood.

Adult↗
PubMed2001

Is population bone mineral density variation linked to the marker D11S987 on chromosome 11q12-13?

Our purpose is to test linkage of human chromosome 11q12-13 to BMD variation. Chromosome 11q12-13 has been linked to three BMD-related phenotypes that are inherited as Mendelian traits in human pedigrees: an autosomal dominant high bone mass trait, autosomal recessive osteoporosis pseudoglioma, and autosomal recessive osteopetrosis. A sibling pair study with 374 sibships showed significant linkage of D11S987 to normal BMD variation, with a maximum logarithm of odds score of 3.5. However, a subsequent linkage study with a total of 595 sibling pairs demonstrated reduced significance for linkage of D11S987 to bone mineral density variation, with a logarithm of odds score less than 2.2. We genotyped five markers in a genomic region of approximately 27 cM centering on D11S987 and measured bone mineral density and other traits (weight, etc.) for 635 individuals from 53 human pedigrees. Each of these pedigrees was ascertained through a proband with bone mineral density Z-scores less than -1.28 at the hip or spine. Adjusting for age, sex, and weight as covariates, we performed two-point and multipoint linkage analyses using the variance component linkage analysis method implemented in Sequential Oligogenic Linkage Analysis Routines. We found little evidence of linkage of these five markers to bone mineral density at the spine, hip, wrist and total body bone mineral content. The maximum logarithm of odds score at these five markers was 0.25, and the maximum logarithm of odds score at D11S987 was 0.15. Therefore, although we cannot exclude the linkage of D11S987 region to bone mineral density variation, there is no evidence for linkage of the marker D11S987 on human chromosome 11q12-13 to bone mineral density variation in our study population.

Adult↗
PubMed1997

All-trans retinoic acid inhibits dexamethasone-induced ALP activity and mineralization in human osteoblastic cell line SV HFO.

We have recently established a human osteoblastic cell line (SV-HFO) in a culture system, in which the cells are mineralized by treatment with dexamethasone (Dex). Using this system, we examined the effects of all trans-retinoic acid (RA) on the mineralization of the cells. RA inhibited the mineralization, coincident with the inhibition of alkaline phosphatase (ALP). On the other hand, RA induced osteocalcin secretion and had no effect on the expression of the other osteoblastic markers such as type I collagen and osteonectin. To further clarify the mechanism of inhibition of mineralization by RA, we used the retinoic acid receptor (RAR) alpha-selective (Am80), beta-selective (CD2019) and gamma-selective (CD437) agonists instead of RA. RAR alpha- and RAR beta-selective agonists inhibited the mineralization and ALP activity of the cells, while the RAR gamma-selective agonist had no such effects. On the other hand, the RAR gamma-selective agonist induced osteocalcin secretion, but RAR alpha- and RAR beta-selective agonists had no effect on osteocalcin secretion. These results suggested that the inhibitory effect of RA on the mineralization of human osteoblasts is mediated by the activation of RAR alpha and/or RAR beta and that RAR gamma preferentially regulates the expression of osteocalcin without influence on mineralization.

Alkaline Phosphatase↗
PubMed2006

Effect of exercise on bone mineral density and lean mass in postmenopausal women.

PURPOSE: To evaluate the effects of physical activity on bone mineral density, bone mineral content, and lean mass in postmenopausal, overweight/obese women. METHODS: We conducted a 12-month randomized controlled aerobic exercise intervention versus control in 173 sedentary, overweight/obese, postmenopausal women, aged 50-75 yr. The exercise prescription consisted of >or=45 min of moderate-intensity aerobic exercise (60-75% of maximal heart rate), 5 d.wk for 12 months. Control participants attended 45-min stretching sessions once a week. Ninety-eight percent (N=170) completed the trial. Exercisers averaged 172 min.wk (SD=89) of exercise and expended 3828 kJ.wk (SD=2053). We assessed body fat, total lean mass, and total body bone mineral density and content using dual-energy x-ray absortiometry (DXA). We compared baseline with 12-month changes in exercisers versus controls. RESULTS: Exercisers lost significantly more weight than stretchers (1.3-kg loss vs 0.1-kg gain, P=0.01). However, no differences between exercisers and controls in the change from baseline to 12 months were detected: exercisers' average bone mineral density increased by 0.005 g.cm and controls' by 0.003 g.cm (P=0.61). Similarly, no significant differences were detected for bone mineral content. Lean mass increased by 0.2 kg in both groups (P=0.84). CONCLUSION: Overall, the results from this randomized controlled study suggest that a yearlong moderate-intensity aerobic exercise intervention does not affect total body bone mineral density, bone mineral content, or lean mass in overweight/obese postmenopausal women.

Aged↗
PubMed1996

A portable system for measuring bone mineral density in the pre-term neonatal forearm.

Current systems used to measure bone mineral content (BMC) in the neonate have the major drawback that the child must be well enough to be moved to the scanner. Consequently, low birth weight pre-term neonates, a group at particular risk of mineral compromise, cannot be measured. This paper describes a portable neonatal bone mineral device capable of measuring bone mineral in the incubator. It uses a radiation sensitive, charge coupled device (CCD) to acquire a bone mineral image enabling bone mineral to be measured at various sites. It measures bone mineral density (BMD) with a precision of 5.5 mg cm-2 in vivo, reduced to 7.5 mg cm-2 when repositioning between scans is taken into account. The procedure takes under 5 min with an image acquisition time of 30 s and an absorbed radiation dose to skin of 6 microSv. Calibration has been undertaken with aluminium foils of differing thickness to confirm the linearity of the system throughout the intended measurement range. A regression line fitted to the data demonstrated linearity and correlation between BMD and aluminium thickness with r = 0.99 (p < 0.0001). Preliminary measurements on pre-term neonates show values of BMD ranging from 43 to 115 mg cm-2 in babies aged 23-41 weeks post-conception. These figures are within the linear range of the system.

Absorptiometry, Photon↗
PubMed1990

[Bone mineral contents of lumbar vertebrae in postmenopausal women--using a quantitative computed-tomography method].

We measured bone mineral contents of lumbar vertebrae (L1, L2, L3, L4) in 58 post-menopausal female volunteers (49-76 years old), using a quantitative computed-tomography method. We investigated age-related changes of bone mineral content, and analyzed the relation of bone mineral content to vertebral deformity and to physical characteristics. The following results were obtained: (1) There were highly significant correlations and some significant differences among bone mineral contents of L1, L2, L3 and L4. (2) Bone mineral content showed an apparently linear decline with age. (3) A significant negative correlation was observed between bone mineral content and the central deformity index of the vertebral body, but not for the anterio-posterior deformity index. (4) It was difficult to verify an association of bone mineral content with physical characteristics, such as height, weight, and body mass index.

Aged↗
PubMed2006

Personality traits in miners with past occupational elemental mercury exposure.

In this study, we evaluated the impact of long-term occupational exposure to elemental mercury vapor (Hg0) on the personality traits of ex-mercury miners. Study groups included 53 ex-miners previously exposed to Hg0 and 53 age-matched controls. Miners and controls completed the self-reporting Eysenck Personality Questionnaire and the Emotional States Questionnaire. The relationship between the indices of past occupational exposure and the observed personality traits was evaluated using Pearson's correlation coefficient and on a subgroup level by machine learning methods (regression trees). The ex-mercury miners were intermittently exposed to Hg0 for a period of 7-31 years. The means of exposure-cycle urine mercury (U-Hg) concentrations ranged from 20 to 120 microg/L. The results obtained indicate that ex-miners tend to be more introverted and sincere, more depressive, more rigid in expressing their emotions and are likely to have more negative self-concepts than controls, but no correlations were found with the indices of past occupational exposure. Despite certain limitations, results obtained by the regression tree suggest that higher alcohol consumption per se and long-term intermittent, moderate exposure to Hg0 (exposure cycle mean U-Hg concentrations > 38.7 < 53.5 microg/L) in interaction with alcohol remain a plausible explanation for the depression associated with negative self-concept found in subgroups of ex-mercury miners. This could be one of the reason for the higher risk of suicide among miners of the Idrija Mercury Mine in the last 45 years.

Adult↗
PubMed2006

Peri-prosthetic bone mineral density after total knee arthroplasty. Cemented versus cementless fixation.

We compared peri-prosthetic bone mineral density between identical cemented and cementless LCS rotating platform total knee arthroplasties. Two matched cohorts had dual energy x-ray absorptiometry scans two years post-operatively using a modified validated densitometric analysis protocol, to assess peri-prosthetic bone mineral density. The knee that was not operated on was also scanned to enable the calculation of a relative bone mineral density difference. Oxford Knee and American Knee Society scores were comparable in the two cohorts. Statistical analysis revealed no significant difference in absolute, or relative peri-prosthetic bone mineral density with respect to the method of fixation. However, the femoral peri-prosthetic bone mineral density and relative bone mineral density difference were significantly decreased, irrespective of the method of fixation, particularly in the anterior distal portion of the femur, with a mean reduction in relative bone mineral density difference of 27%. There was no difference in clinical outcome between the cemented and cementless LCS total knee arthroplasty. However, both produce stress-shielding around the femoral implants. This leads us to question the use of more expensive cementless total knee components.

Absorptiometry, Photon↗
PubMed2005

Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty.

UNLABELLED: Few studies of the VDR polymorphisms have looked at calcium metabolism or long-term effects. We measured bone mineralization and calcium metabolic parameters longitudinally in a group of 99 adolescents. We found a significant relationship between calcium absorption and skeletal calcium accretion and the Fok1, but not other VDR or related, genetic polymorphisms. It seems that the Fok1 polymorphism directly affects bone mineralization during pubertal growth through an effect on calcium absorption. INTRODUCTION: There are few data regarding the relationship between genetic markers for low bone mass and changes in calcium metabolism in childhood or adolescence. We sought to identify the effects of polymorphisms of the vitamin D receptor (VDR) on calcium and bone mineral metabolism in a longitudinal study of pubertal adolescents. MATERIALS AND METHODS: Adolescents (n = 99) received comprehensive stable isotope studies of calcium absorption, bone calcium kinetics, and bone mineralization. Studies were repeated 12 months later. Polymorphisms of putative genetic markers were determined and related to bone mineralization and calcium metabolic finding. Results were analyzed by ANOVA in which changes over time were determined using the initial value as a covariate. RESULTS: Polymorphisms of the Fok1 gene of the VDR were significantly related to calcium absorption (p = 0.008) and whole body BMC (p = 0.03) and BMD (p = 0.006). The Fok1 effect on whole body BMD was significant for those with Ca intake >800 mg/day (p < 0.001), whereas for those with Ca intake < or = 800 mg/day, the Fok1 genotype did not have a significant effect on whole body BMD (p = 0.40). The Fok1 genotype was significantly related to the changes during the year in whole body calcium accretion, with the ff genotype having a 63 +/- 20 mg/day deficit compared with the FF genotype (p = 0.008). CONCLUSIONS: The Fok1 polymorphism of the VDR receptor seems to directly affect bone mineral accretion during pubertal growth through an effect on calcium absorption. The relationship between different genetic polymorphisms and bone mineral metabolism may vary by life stage as well as diet.

Analysis of Variance↗
PubMed1997

Fat or lean tissue mass: which one is the major determinant of bone mineral mass in healthy postmenopausal women?

The relative importance of fat and lean tissue mass in determining bone mineral mass among postmenopausal women was examined in this 1-year longitudinal study. Fifty postmenopausal Caucasian women entered the study; 45 of them completed a 1-year follow-up. Dual-energy X-ray absorptiometry was employed for measuring total and regional bone mineral density (BMD) and bone mineral content (BMC), fat tissue mass (FTM), lean tissue mass (LTM), and body weight. Results from linear regression analysis using the cross-sectional data (n = 50) of the study indicated that LTM explained a larger percentage of variation in bone mineral mass than did FTM. FTM and LTM were found to be moderately correlated (r = 0.55); when FTM was entered in the same predicting regression models, LTM was a significant predictor (p < 0.05) of the total and regional BMC, but not BMD. The percent FTM (and inversely %LTM) was correlated with BMD and BMC, but significant correlation was primarily found only for total body BMD (or BMC). Weight was the best predictor of total body BMD and BMC. Longitudinally (n = 45), annual changes in both FTM and weight were significantly associated with annual changes in regional BMD after adjustment for initial bone mineral values (p < 0.05). We conclude that bone mineral mass is more closely related to LTM than to FTM, while annual changes in regional BMD are more closely correlated with changes in FTM in healthy postmenopausal women. Meanwhile, increased body weight is significantly associated with increased bone mineral mass.

Absorptiometry, Photon↗
PubMed1999

Intermittent and continuous administration of the bisphosphonate ibandronate in ovariohysterectomized beagle dogs: effects on bone morphometry and mineral properties.

Bisphosphonates have emerged as a valuable treatment for postmenopausal osteoporosis. Bisphosphonate treatment is usually accompanied by a 3-6% gain in bone mineral density (BMD) during the first year of treatment and by a decrease in bone turnover. Despite low bone turnover, BMD continues to increase slowly beyond the first year of treatment. There is evidence that bisphosphonates not only increase bone volume but also enhance secondary mineralization. The present study was conducted to address this issue and to compare the effects of continuous and intermittent bisphosphonate therapy on static and dynamic parameters of bone structure, formation, and resorption and on mineral properties of bone. Sixty dogs were ovariohysterectomized (OHX) and 10 animals were sham-operated (Sham). Four months after surgery, OHX dogs were divided in six groups (n = 10 each). They received for 1 year ibandronate daily (5 out of 7 days) at a dose of 0, 0.8, 1.2, 4.1, and 14 microg/kg/day or intermittently (65 microg/kg/day, 2 weeks on, 11 weeks off). Sham dogs received vehicle daily. At month 4, there was a significant decrease in bone volume in OHX animals (p < 0.05). Doses of ibandronate >/= 4.1 microg/kg/day stopped or completely reversed bone loss. Bone turnover (activation frequency) was significantly depressed in OHX dogs given ibandronate at the dose of 14 microg/kg/day. This was accompanied by significantly higher crystal size, a higher mineral-to-matrix ratio, and a more uniformly mineralized bone matrix than in control dogs. This finding lends support to the hypothesis that an increase in secondary mineralization plays a role in gain in BMD associated with bisphosphonate treatment. Moreover, intermittent and continuous therapies had a similar effect on bone volume. However, intermittent therapy was more sparing on bone turnover and bone mineral properties. Intermittent therapy could therefore represent an attractive alternative approach to continuous therapy.

Animals↗
PubMed2003

The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis.

In a recent study of women with postmenopausal osteoporosis, treatment with teriparatide for a median of 19 months increased bone mineral density and decreased the risk of vertebral and nonvertebral fractures. Using the same cohort, the current study evaluated the relationship between these therapeutic effects and the patient's baseline age, vertebral bone mineral density, and prevalent vertebral fractures. In women over 65 years of age, treatment resulted in a greater increase in vertebral bone mineral density than in younger women (treatment-by-age interaction, p = 0.037), but baseline age had no effect on the relative risk reduction for vertebral fractures (treatment-by-age interaction, p = 0.558). In women receiving placebo (with calcium and vitamin D), there was an inverse relationship between baseline vertebral bone mineral density and vertebral fracture risk. When compared across bone mineral density tertiles, the effects of teriparatide on the relative risk for developing new vertebral fractures and increase in vertebral bone mineral density did not differ significantly (p = 0.817 and p = 0.615, respectively). Teriparatide treatment significantly decreased vertebral fracture risk in patients with a vertebral bone mineral density T score of less than -33 or a score between -2.1 and -3.3 (p < 0.001 and p = 0.027, respectively) and showed a trend toward reduced fracture risk in the group with a T score greater than -2.1 (p = 0.115). Placebo-treated women with two or more prevalent vertebral fractures had a significantly greater risk of developing new vertebral fractures than women with zero or one prevalent vertebral fracture (p < 0.001). When compared within prevalent vertebral fracture subgroups, the effects of teriparatide on the relative risk for developing new vertebral fractures were similar. The results of this study indicate that teriparatide offers clinical benefit to patients across a broad range of age and disease severity.

Adult↗