Development of the human medullary arcuate nucleus from mid-gestation to the perinatal period: A morphometric study.

INTRODUCTION: Development of the human medullary arcuate nucleus (AN) has not been sufficiently investigated. The present study provides morphometric data by examining the brains from preterm and perinatal infants. MATERIALS AND METHODS: Nine brains were obtained from infants aged 21-43 postmenstrual weeks (PW). Serial celloidin sections were cut and stained using the Klüver-Barrera method. After microscopic observations, morphometric parameters [AN volume, numerical density (Nv) and total number (Nt) of neurons, and neuronal profile area (PA)] were analyzed. RESULTS: The AN was found as a pair of neuronal masses on the ventral medullary surface at 21 PW. Caudally, it was ventrolateral to the pyramidal tract (PT), and rostrally, medial to the PT. In the middle, it was diminished in size or interrupted. The AN neurons were gradually enlarged with age, showing multiplicity in size and shape. The following findings had a marked asymmetry and individual variability: (1) complete or partial inclusion of the AN in the PT; (2) connection between the rostral AN and the pontine nuclei; (3) coexistence of pyknotic neurons. The AN volume increased exponentially with age, while the Nv decreased exponentially. The Nt changed along two phases (decrease-increase) after mid-gestation. The mean PA increased linearly with age. Asymmetry and/or individual variability were demonstrated in the AN volume, Nt, and mean PA. CONCLUSIONS: Asymmetry and individual variability in the AN morphology are present in fetal period. The AN may undergo neuron death and neuroblasts production in tandem after mid-gestation.

Development of the human perihypoglossal nuclei from mid-gestation to the perinatal period: A morphological study.

INTRODUCTION: Morphological data on the development of the human perihypoglossal nuclei (PHN) are scarce. This study describes the morphology of the human PHN from mid-gestation to the perinatal period. MATERIALS AND METHODS: Ten brains were collected from infants aged 21-43 postmenstrual weeks (PW). Serial sections were cut and stained using the Klüver-Barrera method. Morphometric parameters [volume, neuronal numerical density (Nv) and total number (Nt), and neuronal profile area (PA)] were analyzed from microscopic observations. RESULTS: Four PHN [nucleus of Roller (RO), interfascicular nucleus (IF), intercalated nucleus (IC), and prepositus nucleus (PR)] were identified at 21 PW. Medium-sized to large, oval, or polygonal neurons were concentrated in the ventral nuclei (RO and IF) and localized regions near the IC-PR transition of the dorsal nuclei (IC and PR). Small to large neurons of various shapes were scattered across the dorsal nuclei. The PR showed rostrocaudal differences in the neuronal cytoarchitecture. The volume of each nucleus increased between 21 and 43 PW, with a typical exponential increase for the dorsal nuclei. The Nv in each nucleus exponentially decreased, whereas the Nt was almost stable. The median PA linearly increased for every nucleus, and the increasing rates were greater for the ventral nuclei than those for the dorsal nuclei. CONCLUSIONS: The dorsal and ventral PHN are identifiable at mid-gestation. The topographic relationships of the four nuclei are conserved until the perinatal period. The characteristic neuronal cytoarchitecture of each group is rapidly formed by 28-30 PW.

Development of the human hypoglossal nucleus from mid-gestation to the perinatal period: A morphological study.

INTRODUCTION: The human hypoglossal nucleus (nXII) was morphologically examined from mid-gestation to the perinatal period. MATERIALS/METHODS: Serial brain sections from 6 preterm and 4 perinatal infants aged 21-43 postmenstrual weeks (PW) were stained with the Klüver-Barrera method. Following microscopic observation, morphometric parameters (volume, neuronal number, and neuronal profile area [PA]) were analysed. RESULTS: Two types of neurons, motor and non-motor neurons, were observed at 21 PW. The motor neurons were distributed into clusters, which were not completely separated. The non-motor neurons were dispersed among the motor neurons. Myelination of the hypoglossal nerve roots was noted at 21 PW, when degenerated neurons were sporadically encountered. To a lesser extent, they were seen until 35 PW. The nXII volume increased exponentially with age. Conversely, the neuronal numerical density decreased exponentially, while the total number remained relatively stable. The neuronal PA increased gradually, with a greater rate of increase measured in the caudal part. CONCLUSIONS: In the human nXII, motor and non-motor neurons are distinguishable from mid-gestation. Then, while the nXII expands exponentially in volume, the two types of neurons change in number and PA almost in parallel during the second half of gestation. Natural neuronal death may also occur.

Development of the human accessory olivary nuclei: A morphometric and computerized 3D-reconstruction study.

INTRODUCTION: This study described the prenatal development of the accessory olivary nuclei (AO) in humans. MATERIALS/METHODS: Serial brain sections from ten pre- and full term infants aged 21-43 postmenstrual weeks (PW) were stained using the Klüver-Barrera method. A computerized 3D-reconstruction technique and morphometry were adopted for the study. RESULTS: The medial AO (MAO) and dorsal AO (DAO) were identified at 21 PW. The dorsal cap was clearly differentiated from the main body (MB) of the MAO in neuronal cytoarchitecture. Pyknotic neurons were diffusely observed in the AO at 21 PW and were most concentrated in the MB. These neurons became infrequent from 28 PW onward. Neuronal nests existed in clusters between the AO and the medial lemniscus at 21 PW, which reduced progressively in size and number with age. The 3D-reconstructions showed that the AO are separated into caudal and rostral parts, and that this separation is achieved by mid-gestation in the DAO. Nuclear volume increased exponentially with age in the AO, although the rate of increase was half that of the principal nucleus (PO). Neuronal numerical density decreased rapidly 21-28 PW. The total neuronal number showed a weak correlation with age. The mean neuronal profile area increased linearly with age. CONCLUSION: The human AO are separated into caudal and rostral parts in the fetal period. The nuclear volume and neuronal profile areas increase with age, although the rate of this increase is lower than in the PO. Natural neuronal death may occur at mid-gestation in the AO.

Development of the human principal inferior olivary nucleus: A morphometric and computerized 3D-reconstruction study.

INTRODUCTION: This study describes the prenatal development of the principal inferior olivary nucleus (PO) in humans. MATERIAL/METHODS: Ten brains were obtained from preterm infants aged 21-43 postmenstrual weeks (PW). After fixation, the brains were processed into 30-µm serial sections, which were stained using the Klüver-Barrera method. RESULTS: At mid-gestation, the dorsal and ventral lamellae were distinguishable. The dorsal lamella (DL) was composed of ballooned and folded portions, with many neurons peripherally gathered in the ballooned portion, and neurons densely packed in the folded portion. Clusters of pyknotic neurons were observed in the lateral portion of the PO at 21PW. The PO acquired thin complicated folds by 28-29 PW. Then, it regained the width of a nuclear band, and further elaborated the folds. The 3D-reconstruction models showed that the basic pattern of folding like in adults was attained at 28-29PW, and that the rostro-medial region of DL was microgyric. The nuclear volume increased exponentially with age. The total surface area increased progressively, while the surface density varied in a biphasic manner, wherein it increased initially and then decreased. The neuronal profile area increased uniformly. The total neuronal number increased uniformly, while the numerical density decreased rapidly during 21-29 PW. CONCLUSION: After mid-gestation, the period of 21-29 PW may be critical, because the PO undergoes extensive folding after massive neuronal death.

Development of the human lateral geniculate nucleus: A morphometric and computerized 3D-reconstruction study.

INTRODUCTION: The lateral geniculate nucleus (LGN) is the major relay center of the visual pathway in humans. There are few quantitative data on the morphology of LGN in prenatal infants. In this study, using serial brain sections, the author investigated the morphology of this nucleus during the second half of fetal period. MATERIAL AND METHODS: Eleven human brains were obtained at routine autopsy from preterm infants aged 20-39 postmenstrual weeks. After fixation, the brain was embedded en bloc in celloidin and cut serially at 30 µm in the horizontal plane. The sections were stained at regular intervals using the Klüver-Barrera method. RESULTS: At 20-21 weeks, the long axis of LGN declined obliquely from the vertical to horizontal plane, while a deep groove was noted on the ventro-lateral surface of the superior half. At this time, an arcuate cell-sparse zone appeared in the dorso-medial region, indicating the beginning of lamination. From 25 weeks onwards, the magnocellular and parvocellular layers were distinguishable, and the characteristic six-layered structure was recognized. The magnocellular layer covered most of the dorsal surface, and parts of the medial, lateral, and inferior surfaces but not the ventral and superior surfaces. Nuclear volume increased exponentially with age during 20-39 weeks, while the mean neuronal profile area increased linearly during 25-39 weeks. CONCLUSION: Human LGN develops a deep groove on the ventro-lateral surface at around mid-gestation, when the initial lamination is recognized in the prospective magnocellular layer. Thereafter, the nuclear volume increases with age in an exponential function.

Development of the human oculomotor nuclear complex: Centrally-projecting Edinger-Westphal nucleus.

BACKGROUND: The cytoarchitecturally defined Edinger-Westphal nucleus (EW) is now referred to by many investigators as the centrally-projecting EW (EWcp) in humans. Although the mature structure is well-characterized, there have been few reports describing the precise morphology of this nucleus during the second half of gestation. SUBJECTS/DESIGN: Eleven brains were examined from preterm infants, aged 20-39 postmenstrual weeks, who died of various causes. After fixation, the brains were embedded in celloidin and serial sections of 30-µm thickness were cut in the horizontal plane. Sections were stained using the Klüver-Barrera method. In addition to microscopic observations, computerized 3D reconstruction and morphometry were performed. RESULTS: From 21 weeks, the EWcp had a distinctive, complex 3D structure comprising two or three parts. The dorsal part was arcuate, half encircling the oculomotor somatic nuclei (OSN). The rostral part was the most voluminous, ventral to the rostral OSN, extending anteriorly. The caudal part was the smallest, and was composed of several neuronal groups near the ventral tip of the OSN. In three cases, the caudal part was absent. It could also be joined to the rostral part, forming a ventral part. The total volume of the EWcp increased exponentially with age, and the ventral part grew more rapidly than the dorsal part. The mean neuronal profile area increased linearly with age, and the rate of increase was almost equal between the dorsal and ventral parts. CONCLUSIONS: This study suggests that a distinctive, complex, two- or three-part 3D structure of the EWcp is preserved after mid-gestation, and that the ventral part of the EWcp may expand in volume more rapidly than the dorsal part.

Development of the human oculomotor nuclear complex: somatic nuclei.

BACKGROUND: Precise anatomical data on the development of human oculomotor somatic nuclei (OSN) remain rare. DESIGN/SUBJECTS: This study describes the histology of human OSN in 11 preterm and full-term infants aged 20-43 postmenstrual weeks who died of various causes. Celloidin-embedded serial sections were stained with the Klüver-Barrera and other conventional methods including silver impregnation. To evaluate the growth of OSN quantitatively, the author estimated the nuclear volume and the average neuronal area on morphometry. RESULTS: Four subnuclei were identified at 20-21 weeks: the fascicular, principal, dorsal median, and ventral median nucleus. Early tigroid Nissl bodies appeared in presumed motoneurons by 27-28 weeks, then resembled adult Nissl bodies at birth. On silver impregnation, the oculomotor nerve roots, crossed or uncrossed fibers at the midline, and a plexus of efferent or afferent axons in the neuropil were observed at 20-21 weeks. Then, the plexus was elaborated to form a perineuronal net of thin axon terminals by 28-29 weeks. The nuclear volume of OSN exponentially increased with age over 20-43 weeks, while the average of neuronal profile areas linearly increased in each subnucleus; the coefficient of regression was largest in the principal nucleus, and the regression lines nearly overlapped among the other subnuclei. Statistical analysis confirmed that the average neuronal area was largest in the principal nucleus in older cases. CONCLUSION: This study suggests that four subnuclei can be distinguished in human OSN by mid gestation, and that the principal nucleus may be different in neuronal cytoarchitecture from the others.

Maternal-to-fetal transfer and concentration profiles of PCB congeners for Steller sea lions (Eumetopias jubatus) from Hokkaido, Japan.

The concentrations of PCB congeners in the blubber and liver of mother Steller sea lions (Eumetopias jubatus; SSLs) and their fetuses from the coast of Hokkaido, Japan in 2008, 2010 and 2012 were analyzed by HRGC-HRMS, in order to elucidate PCB congener profiles and maternal-to-fetal transfer of PCBs in SSLs. ΣPCBs in the fetuses were 1400 ± 660 (the mean ± SD) ng/g-fat in the blubber and 570 ± 320 ng/g-fat in the liver, respectively. There was a concern that SSLs had been contaminated by PCBs during the fetal period. The concentrations of the major congeners in the blubber and liver were a correlation between the fetus and mother (blubber: r=0.9934, liver: r=0.9160; P ≦ 0.05). The results indicated that PCBs in the fetuses came from the mothers. #177 and #199 showed no correlations between the fetus and the mother in the blubber and liver. This indicated a selective capture by some natural protector such as the placenta.

An acardiac twin with advanced development of the brain: a histologic and volumetric study.

We describe a rare case of an acardiac twin (acardius anceps) with advanced brain development. Complete serial sections of the brain were made for microscopic observation and volumetric analysis. The cerebral surface showed unusual gyri and sulci with absence of the right olfactory bulb. Cortical lamination was almost normal, except for the insula where polymicrogyria and leptomeningeal neuroglial heterotopia were seen. The latter was also observed in the basal forebrain. Partial agenesis of the corpus callosum was noted with a very thick left cingulate gyrus. The anterior commissure did not cross the midline. Subcortical structures including basal ganglia, diencephalon, and brainstem/cerebellum appeared grossly normal, but hypo- or dysplasic changes were observed in some regions. The ventricles were enlarged and the left internal carotid artery was absent. In addition, porencephalic foci were located in the right temporal and parietal lobes. On comparative volumetry, the total brain was normal, but brain structures showed variable volumetric changes, with higher volume in the ventricles, diencephalon, and archi-/paleopallium, and lower volume in the periventricular germinal layer, basal ganglia, cerebral cortex, and brainstem/cerebellum. These observations showed that brain development can proceed nearly normally in acardia if blood flow is relatively preserved.

Concentration profiles of PCB congeners in the blubber and liver of Steller sea lions (Eumetopias jubatus) from the coast of Hokkaido, Japan.

The concentrations of PCB congeners in the blubber and liver of male and female Steller sea lions (Eumetopias jubatus; SSLs) collected from the Shakotan Peninsula and the Nemuro Strait, Hokkaido, Japan in 2008 and 2010 were measured by HRGC-HRMS, in order to express the concentration profiles in SSLs at these regions. #153 predominated in both organs, followed by #138, #99 and #118. In males, #28 and #31 were concentrated particularly in the blubber, while #177 and #199 were accumulated specifically in the liver. The differences in these concentration profiles might be expressed by the differences in the organs and their functions. The concentrations of #99, #118, #138, #153, and #180 in the blubber appeared to correspond significantly with the differences between genders. The details of the surveys on PCB congeners in SSLs could clarify the differences in the residue levels of individual congeners for organs and genders.

Development of the human abducens nucleus: a morphometric study.

BACKGROUND: The abducens nucleus directly innervates the lateral rectus muscle and plays a role in controlling conjugate horizontal eye movements. Although the neuronal cytoarchitecture of the abducens nucleus has been extensively investigated in various species of vertebrates, few studies have been undertaken in humans, especially in fetuses or neonates. DESIGN/SUBJECTS: We examined 12 human brains from preterm infants aged 20-43 postmenstrual weeks to document the histology and morphometry of the abducens nucleus. The brain was processed into celloidin-embedded serial sections stained with the Klüver-Barrera and other conventional methods. RESULTS: The nucleus was identified as a mass of cells as early as 20 weeks. Its neurons were clearly distinguished from glial cells due to droplet-like, clear nuclei containing prominent nucleoli and surrounded by a basophilic perikaryon. Neurons of various sizes and shapes were intermingled within the nucleus, although larger neurons were located towards the center of the nucleus. Immature granular or reticular Nissl bodies were seen at 20-21 weeks. Tigroid, coarse Nissl bodies appeared around 28-29 weeks in larger neurons, although in smaller neurons Nissl bodies were dispersed or concentrated peripherally. Morphometric results were: (1) the nuclear volume exponentially increased with age between 20 and 43 weeks; (2) the histograms of neuronal profile areas showed a non-normal distribution trailing toward the right and widening with age; (3) the geometric average of neuronal profile areas increased linearly with age. CONCLUSION: Our study suggests that the human abducens nucleus enlarges more quickly toward the end of gestation, and comprises heterogeneous groups of neurons.

Determination of dioxin concentrations in fish and seafood samples using a highly sensitive reporter cell line, DR-EcoScreen cells.

There is a strong need for the development of relatively rapid and low-cost bioassays for the determination of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (dl-PCBs) in environmental and food samples. In this study, we applied a reporter gene assay using DR-EcoScreen cells (DR-cell assay), which is highly sensitive to dioxins, to the determination of PCDD/Fs and dl-PCBs in fish and seafood samples. The PCDD/Fs and dl-PCBs were extracted from homogenated samples (10 g) of 30 fish and shellfish, purified by clean-up procedure using a multilayered silica gel column and an alumina column, and applied to DR-cell assay. Interestingly, the bioanalytical equivalent (BEQ) values obtained from the DR-cell assay [<0.1∼5.4 pg BEQ g(-1) wet weight (ww)] were closely correlated with the toxicity equivalent (TEQ) values from conventional high-resolution gas chromatography/high-resolution mass spectrometry (HRGC-HRMS) analysis (r(2)=0.912), and the slope of regression line was 0.913. Therefore, we multiplied the BEQ values from the DR-cell assay by a conversion coefficient (1.095, the reciprocal of 0.913) to approximate the TEQ values from the HRGC-HRMS analysis. Furthermore, we used this DR-cell assay to perform a prescreening test of PCDD/Fs and dl-PCBs in 16 fish and seafood samples purchased from a supermarket, revealing that a sample from the fatty flesh of a bluefin tuna exceeded 8 pg TEQ g(-1)ww (the European Union-tolerance limit). Taken together, these results suggest that the DR-cell assay might be applicable as a rapid and low-cost prescreening method to determine dioxin levels in fish and seafood samples.

Development of the human trochlear nucleus: a morphometric study.

BACKGROUND: The trochlear nucleus, the smallest of the extraoculomotor nuclei, is unique or even curious, because the nerve roots emerge dorsally from the superior medullary velum after decussation. Little information is available on the developmental anatomy of this nucleus in humans. DESIGN/SUBJECTS: We examined serial brain sections from 10 premature infants aged 20-39 weeks of gestation to document the histology and morphometry. RESULTS: The trochlear nucleus was composed of three parts: the rostral tip, the main body, and the caudal division. The rostral tip was a rostral continuation of the main body, being closely related to the oculomotor nucleus; the main body was enveloped by a fibrous capsule; the caudal division was a small separate cluster of neurons in the medial longitudinal fasciculus or the root fibers with individual variations. Tigroid Nissl bodies first appeared at 28 weeks in presumed motoneurons. Various sizes of motoneurons were recognized; medium-sized to small motoneurons were preferentially accumulated in the rostral tip. Among the motoneurons, presumed non-motor neurons were infrequently scattered. Morphometric analysis showed that the nuclear volume exponentially increased with age, about 15 fold over 20-39 weeks, while the average profile area of the neurons linearly increased. Statistical analysis confirmed that cell area was smallest in the rostral tip among the three parts. CONCLUSION: Although the sample number is small in this study, it suggests that the human trochlear nucleus can be divided into three parts, and that the overall growth may be accelerated at about 30 weeks of gestation.

Application of a bioassay using DR-EcoScreen cells to the determination of dioxins in ambient air: a comparative study with HRGC-HRMS analysis.

There is a strong need for the development of relatively rapid and low-cost bioassays for the determination of dioxins (polychlorinated dibenzo-p-dioxins, dibenzofurans, and dioxin-like polychlorinated biphenyls) in environmental and food samples. In this study, we applied a bioassay system using highly sensitive DR-EcoScreen cells (DR-cell assay) to the determination of low levels of dioxins in ambient air samples. The dioxins from 80 ambient air samples were extracted, purified by cleanup procedure, and applied to both DR-cell assay and high-resolution gas chromatography/high-resolution mass spectrometry (HRGC-HRMS) analysis. Interestingly, the toxic equivalents (TEQ) values obtained from the DR-cell assay were closely correlated with those from the HRGC-HRMS analysis (r2 = 0.957). Although the cell-based TEQ values were relatively (3.66-fold) higher than the TEQ values from the HRGC-HRMS analysis, this discrepancy was thought to be due to the difference between the toxic equivalency factor (TEF) and the relative potency (DR-REP) determined for individual dioxins. Therefore, we multiplied the TEQ values from the DR-cell assay by a conversion coefficient (0.273, the reciprocal of 3.66) and could approximate the values from the HRGC-HRMS analysis. These results clearly suggest at the DR-cell assay might be a promising method for the rapid and low-cost screening of dioxins in ambient air samples.

Development of the human parvocellular red nucleus. A morphological study.

Morphology of the human parvocellular red nucleus (RNp) was investigated in 14 fetuses aged from 12 to 39 weeks of gestation (WG). The brains were processed into celloidin-embedded serial sections. At 12 WG, the anlage of RNp was observed as an ovoid mass of immature neurons clustering into some groups. Lobular appearance in cross-sectional images was conspicuous during the early stages (12-23 WG), particularly at rostral levels. The fasciculus retroflexus of Meynert was seen as a prominent bundle of fibers surrounded by the most rostral part of RNp. Two types of neurons were identified: large and small neurons. Large neurons were earlier observed at 16 WG, and had a polygonal or multipolar perikaryon with abundant Nissl bodies from 28 WG onwards. Small neurons later appeared among large neurons at 21 WG, and had a triangular or ovoid perikaryon with scanty Nissl bodies. The volume of RNp showed an exponential increase with age during 20-39 WG. The mean of neuronal perikaryonal areas showed a linear increase with age in both types during 16-39 WG, although the degree of change was much greater in large neurons than small neurons. The current study has clearly demonstrated the presence of two neuronal populations and their differential growth in developing human RNp.

Development of the human magnocellular red nucleus: a morphological study.

The development of the human magnocellular red nucleus (RNm) was studied in 20 fetuses at 12-39 weeks of gestation (WG). With microscopic observation on serial sections of the brain, we measured the profile area of a neuronal cell body. At 12WG, several islands of immature cells of the RNm appeared dorsal to the parvocellular red nucleus (RNp). At 16WG, the RNm was detected ventral to the RNp as a cluster of semilunar shape, consisting of basophilic neurons of various sizes. During 18-23WG, the neurons were dispersed dorsal to the RNp. They were isolated or aggregated as small clusters among the myelinated oculomotor nerve roots. Twenty-eight WG onwards, the neurons were widely distributed ventrolateral to the superior cerebellar peduncle and around the caudal pole of the RNp. Measurement of the profile area revealed that the average size of overall neurons increased almost linearly with the gestational age, and that two populations (large and small neurons) were clearly distinguished on the histogram from 33WG onwards. The relative position of the RNm to the RNp may vary among the individuals, especially in earlier fetal stage. This study suggests that the differentiation and maturation of neuronal cytoarchitecture of the RNm may gradually and monotonously progress during the later half of gestation.

Efficacy of different dosing schedules of etidronate for stress shielding after cementless total hip arthroplasty.

Forty-four women who had undergone cementless total hip arthroplasty (THA) were selected for determination of the optimum dosage of etidronate in the treatment of stress shielding after surgery. Patients were 55-86 years of age. The patients were randomized into three groups. The control group (n = 17) was not treated with osteoactive drugs. The low-dose group (n = 12) and the high-dose group (n = 15) received 200 mg or 400 mg etidronate daily for 2 weeks, followed by 12 weeks of calcium supplementation of 500 mg/day. These patients received four cycles of therapy over 1 year postoperatively. Periprosthetic bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at 3 weeks, 6 months, and 12 months. At 12 months, bone loss in the low-dose and high-dose groups was significantly lower compared with the control group in Gruen zones 1 and 7. There were additional significant differences with regard to bone loss between the control group and the high-dose group in zones 2, 4, and 6. Our data suggest that high dosages are more effective in reducing postoperative bone loss after cementless THA.

Effects of discontinuation as well as intervention of cyclic therapy with etidronate on bone remodeling after cementless total hip arthroplasty.

We previously reported the effects of cyclic therapy with etidronate (CTE) on periprosthetic bone mineral density (BMD) after cementless total hip arthroplasty (THA). This study aimed to evaluate the effects of withdrawal and intervention of CTE after cementless THA. The control group consisted of 24 patients without osteoactive drugs. Sixteen patients continued on CTE (i.e., 400 mg/day oral etidronate for 2 weeks followed by 12 weeks of 500 mg/day calcium lactate, repeated every 14 weeks) for the first 12 months followed by no treatment for 18 months (early-etidronate group). Fifteen patients received no treatment for the first 18 months followed by CTE for 12 months (late-etidronate group). Periprosthetic BMD in seven regions of interest based on the zones of Gruen et al. was measured with dual energy X-ray absorptiometry at 3 weeks, 6, 12, 18, 24, and 30 months postoperatively. At 12 months after operation (off therapy point in the early-etidronate group), postoperative decreases of BMD in the early-etidronate group were significantly smaller than those in the control group in zones 1, 2, 5, 6, and 7 and those in the late-etidronate group in zones 1, 5, 6, and 7 (P < 0.05 for each). In the early-etidronate group, significant decreases in BMD were found during months 12-30 (off therapy period) after withdrawal of CTE in zones 1 and 7 (P < 0.05 for each). In the late-etidronate group, BMD increased significantly in zones 4 and 6 (P < 0.05 for each) during months 18-30 (on therapy period) after intervention trial, while in the controls, BMD decreased significantly in zone 3 (P < 0.05) over this period. At the final follow-up (30 months), BMD loss in zone 7 was significantly less in the early-etidronate group than in the other groups (P < 0.05). BMD changes in the early-etidronate group and late-etidronate group were associated with changes in biochemical bone markers.

Predictive value of a preoperative biochemical bone marker in relation to bone remodeling after cementless total hip arthroplasty.

To identify the factors predicting proximal bone resorption of the femur after cementless total hip arthroplasty (THA), we studied 24 postmenopausal women with osteoarthritis. Periprosthetic bone mineral density (BMD) measurements of the seven Gruen zones were determined with dual-energy X-ray absorptiometry at 3 wk, 6, 12, and 18 mo after operation. The greatest decrease in BMD (13.2%) was found in zone 7 at 18 mo. At 18 mo, preoperative serum bone alkaline phosphatase was associated univariately with BMD loss in zones 1 (r = 0.407, p = 0.048) and 7 (r = 0.543, p = 0.006) and urinary N-telopeptide cross-linked collagen type I (NTX) was associated univariately with that in zone 7 (r = 0.520, p = 0.009). Patient age correlated with BMD loss in zone 7 (r = 0.425, p = 0.039). Multiple regression analysis identified a significant relationship between the BMD loss and patient age and NTX in zone 7 at 18 mo (r2 = 0.422, p = 0.001). We conclude that preoperative bone markers are significant predictors of bone remodeling after THA with the particular implants used in our study.