Effect of inverted internal limiting membrane flap technique on small-medium size macular holes.

Inverted internal limiting membrane (ILM) flap technique was developed to achieve macular hole (MH) closure in large MH and refractory cases. In this study, we evaluate the effect of the technique for small-medium size MH. We recruited patients who underwent vitrectomy for small-medium size (< 400 µm) MH with either inverted ILM flap technique (flap group) or with conventional ILM peeling (peeling group). Using propensity score, 21 eyes of 21 patients in the peeling group were matched against 21 eyes of 21 patients in the flap group. We compared MH closure rate, postoperative visual acuity, and recovery of the external limiting membrane (ELM) and ellipsoid zone (EZ). The MH closure rate was not different between the two groups (flap vs peeling: 90% vs 100%, P = 0.49). Whereas there was no significant difference in visual acuity improvement between the two groups, the flap group showed more disruption of the ELM 3 months after surgery and of the EZ at 3 and 6 months after surgery (P = 0.02, P = 0.03, and P = 0.04, respectively). The result suggested that inverted ILM flap technique does not have additional benefits for small-medium size MHs and may delay recovery of retinal integrity.

Transcriptional autoregulation of zebrafish tbx6 is required for somite segmentation.

The presumptive somite boundary in the presomitic mesoderm (PSM) is defined by the anterior border of the expression domain of Tbx6 protein. During somite segmentation, the expression domain of Tbx6 is regressed by Ripply-meditated degradation of Tbx6 protein. Although the expression of zebrafish tbx6 remains restricted to the PSM, the transcriptional regulation of tbx6 remains poorly understood. Here, we show that the expression of zebrafish tbx6 is maintained by transcriptional autoregulation. We find that a proximal-located cis-regulatory module, TR1, which contains two putative T-box sites, is required for somite segmentation in the intermediate body and for proper expression of segmentation genes. Embryos with deletion of TR1 exhibit significant reduction of tbx6 expression at the 12-somite stage, although its expression is initially observed. Additionally, Tbx6 is associated with TR1 and activates its own expression in the anterior PSM. Furthermore, the anterior expansion of tbx6 expression in ripply gene mutants is suppressed in a TR1-dependent manner. The results suggest that the autoregulatory loop of zebrafish tbx6 facilitates immediate removal of Tbx6 protein through termination of its own transcription at the anterior PSM.

Deadenylation by the CCR4-NOT complex contributes to the turnover of hairy-related mRNAs in the zebrafish segmentation clock.

In the zebrafish segmentation clock, hairy/enhancer of split-related genes her1, her7, and hes6 encodes components of core oscillators. Since the expression of cyclic genes proceeds rapidly in the presomitic mesoderm (PSM), these hairy-related mRNAs are subject to strict post-transcriptional regulation. In this study, we demonstrate that inhibition of the CCR4-NOT deadenylase complex lengthens poly(A) tails of hairy-related mRNAs and increases the amount of these mRNAs, which is accompanied by defective somite segmentation. In transgenic embryos, we show that EGFP mRNAs with 3'UTRs of hairy-related genes exhibit turnover similar to endogenous mRNAs. Our results suggest that turnover rates of her1, her7, and hes6 mRNAs are differently regulated by the CCR4-NOT deadenylase complex possibly through their 3'UTRs in the zebrafish PSM.

Functional roles of the Ripply-mediated suppression of segmentation gene expression at the anterior presomitic mesoderm in zebrafish.

Somites sequentially form with a regular interval by the segmentation from the anterior region of the presomitic mesoderm (PSM). The expression of several genes involved in the somite segmentation is switched off at the transition from the anterior PSM to somites. Zebrafish Ripply1, which down-regulates a T-box transcription factor Tbx6, is required for the suppression of segmentation gene expression. However, the functional roles of the Ripply-mediated suppression of segmentation gene expression at the anterior PSM remain elusive. In this study, we generated ripply1 mutants and examined genetic interaction between ripply1/2 and tbx6. Zebrafish ripply1-/- embryos failed to form the somite boundaries as was observed in knockdown embryos. We found that somite segmentation defects in ripply1 mutants were suppressed by heterozygous mutation of tbx6 or partial translational inhibition of tbx6 by antisense morpholino. We further showed that somite boundaries that were recovered in tbx6+/-; ripply1-/- embryos were dependent on the function of ripply2, indicating that relative gene dosage between ripply1/2 and tbx6 plays a critical role in the somite formation. Interestingly, the expression of segmentation genes such mesp as was still not fully suppressed at the anterior PSM of tbx6+/-; ripply1-/- embryos although the somite formation and rostral-caudal polarity of somites were properly established. Furthermore, impaired myogenesis was observed in the segmented somites in tbx6+/-; ripply1-/- embryos. These results revealed that partial suppression of the segmentation gene expression by Ripply is sufficient to establish the rostral-caudal polarity of somites, and that stronger suppression of the segmentation gene expression by Ripply is required for proper myogenesis in zebrafish embryos.

Visual outcomes and prognostic factors in open-globe injuries.

BACKGROUND: Ocular trauma is an important cause of visual loss worldwide. Improvements in our knowledge of the pathophysiology and management of ocular trauma during the past 30 years, in conjunction with advances in the instrumentation and techniques of ocular surgery, have improved the efficacy of vitreoretinal surgery in injured eyes. The aim of the current study was to determine the visual outcomes and prognostic factors of open-globe injuries in the Japanese population. METHODS: Retrospective study of 59 eyes of 59 patients presented with open globe injuries between September 2008 and March 2014 at Nagasaki University Hospital was conducted. Demographic factors including age, gender, and clinical data such as cause of injury, presenting visual acuity (VA), location of injury, type of injury, lens status, presence of intraocular foreign body, types of required surgeries, and final VA were recorded. According to the classification of Ocular Trauma Classification Group, wound location was classified into three zones. Chi-square test was used to compare presented data. RESULTS: Out of the 59 patients, 46 were placed in the Light Perception (LP) group, and 13 were placed in the No Light Perception (NLP) group. Work-related trauma was the most common cause (27 eyes) followed by falls (19eyes). Work-related trauma was common in males (P = 0.004), while falls was significantly common in females (P = 0.00001). Zone III injuries had statistically significantly poor prognostic factor compared to other zones (P = 0.04). All cases of NLP group (100%) presented with rupture globe. Poor VA at first visit (P = 0.00001), rupture globe (P = 0.026), history of penetrating keratoplasty (PK) (P = 0.017), retinal detachment (RD) (P = 0.0001), vitreous hemorrhage (VH) (P = 0.044), and dislocation of crystalline lens (P = 0.0003) were considered as poor prognostic factors. CONCLUSION: Poor VA at first visit, rupture globe, zone III injuries, history of penetrating keratoplasty, RD, VH, and dislocation of crystalline lens were found to be poor prognostic factors. PPV had a good prognostic value in open globe injuries associated with posterior segment involvement.

Spontaneous dislocation of the posterior chamber intraocular lens.

AIM: To evaluate the possible risk factors for posterior chamber intraocular lens dislocation either in-the-bag (ITB) dislocation or out-of-the-bag (OOTB) dislocation. METHODS: All subjects who sustained late intraocular lens dislocation from January 2011 until May 2014 and presented to the Nagasaki University Hospital were included in the study. This study is a retrospective evaluation of all cases of posterior chamber intraocular lens dislocation in this defined period. All cases had history of uncomplicated cataract surgery with implantation of posterior chamber intraocular lens. Patients with history of trauma (before cataract surgery) were excluded from the study. The main outcome measures of the study were evaluation of risk factors for dislocation of both groups and determination of the interval between cataract surgery and dislocation. RESULTS: Thirty-six eyes (69.23%) suffered ITB dislocation, and 16 eyes (30.77%) suffered OOTB dislocation. Intraocular lens dislocation was common in males (42 eyes = 80.77%) than females (10 eyes = 19.23%). Patients of ITB dislocation group were significantly older than OOTB dislocation group at the time of initial intraocular lens implantation and at the time of exchange surgery. CONCLUSION: The most prevalent risk factors in both groups were axial myopia in 18 eyes (34.61%), vitreoretinal surgery in 16 eyes (30.77%), and pseudoexfoliation in 13 eyes (25%) in all cases.

Success Rates of Vitrectomy in Treatment of Rhegmatogenous Retinal Detachment.

Aim. To investigate the anatomical success rates of pars plana vitrectomy (PPV) after primary rhegmatogenous retinal detachment (RRD). Methods. This retrospective study was conducted between December 2008 and October 2014 at Nagasaki University Hospital. The preoperative data recorded included the lens status, location of the retinal tear, whether a tear was visualized, presence of multiple tears, macula status, presence of peripheral lattice retinal degeneration, and best-corrected visual acuity (BCVA). The primary outcome measures were anatomical (primary and final) and functional success (visual acuity better than 6/60). Results. This study evaluated 422 eyes of 411 patients with a mean age of 57.7 ± 11.2 years. The single-operation reattachment rate (primary anatomical success) was 89.8%. The final anatomical success rate was 100% after 2-6 operations (mean = 3.14 ± 1.03). Functional success rate after the primary reattachment operation was 96.7%, while it was 97.2% at the end of the follow-up. Multiple logistic regression analysis of the possible risk factors for the primary anatomical failure showed a significant relation with the 25 G instruments (P = 0.002) and the presence of multiple tears (P = 0.01). Conclusion. The primary anatomical success of PPV for primary uncomplicated RRD was 89.8% and the final anatomical success rate was 100%.

Lipoma arborescens arising in the extra-articular bursa of the knee joint.

Lipoma arborescens arising in the extra-articular bursa of the knee joint is extremely rare. We describe an 11-year-old boy who complained of a gradual swelling mass of the lateral knee joint. Magnetic resonance imaging (MRI) showed a high signal intensity tumor on T1- and T2-weighted images with a thickened septa and nodular lesion that showed low signal intensity. The radiologist suggested the possible differential diagnosis of well-differentiated liposarcoma. At operation, the tumor was found under the iliotibial tract and was not in contact with the knee joint. Histopathologically, this lesion was diagnosed as lipoma arborescens arising in the extra-articular bursa of the knee joint. On MRI, the appearance of lipoma arborescens arising in the extra-articular bursa of the knee joint differed from that of conventional intra-articular lipoma arborescens. In this report, we describe a case of extra-articular lipoma arborescens of the knee joint bursa and discuss the diagnosis and etiology.

Induction of Functional 3D Ciliary Epithelium-Like Structure From Mouse Induced Pluripotent Stem Cells.

PURPOSE: To generate ciliary epithelium (CE) from mouse induced pluripotent stem (iPS) cells. METHODS: Recently, a protocol for self-organizing optic cup morphogenesis in three-dimensional culture was reported, and it was suggested that ocular tissue derived from neural ectoderm could be differentiated. We demonstrated that a CE-like double-layered structure could be induced in simple culture by using a modified Eiraku differentiation protocol. RESULTS: Differentiation of a CE-like double-layered structure could be promoted by glycogen synthase kinase 3ß (GSK-3ß) inhibitor. Connexin43 and aquaporin1 were expressed in both thin layers, and induced CE-like cells expressed ciliary marker genes, such as cyclinD2, zic1, tgfb2, aldh1a3, wfdc1, otx1, BMP4, and BMP7. Increases in cytoplasmic and nuclear ß-catenin in aggregates of the CE-like double-layered structure were confirmed by Western blot analysis. In addition, tankyrase inhibitor prevented the induction of the CE-like double-layered structure by GSK-3ß inhibitor. Dye movement from pigmented cells to nonpigmented cells in the mouse iPS cell-derived CE-like structure was observed in a fluid movement experiment, consistent with the physiological function of CE in vivo. CONCLUSIONS: We could differentiate CE from mouse iPS cells in the present study. In the future, we hope that this CE-like complex will become useful as a graft for transplantation therapy in pathologic ocular hypotension due to CE dysfunction, and as a screening tool for the development of drugs for diseases associated with CE function.

Posterior-anterior gradient of zebrafish hes6 expression in the presomitic mesoderm is established by the combinatorial functions of the downstream enhancer and 3'UTR.

In vertebrates, the periodic formation of somites from the presomitic mesoderm (PSM) is driven by the molecular oscillator known as the segmentation clock. The hairy-related gene, hes6/her13.2, functions as a hub by dimerizing with other oscillators of the segmentation clock in zebrafish embryos. Although hes6 exhibits a posterior-anterior expression gradient in the posterior PSM with a peak at the tailbud, the detailed mechanisms underlying this unique expression pattern have not yet been clarified. By establishing several transgenic lines, we found that the transcriptional regulatory region downstream of hes6 in combination with the hes6 3'UTR recapitulates the endogenous gradient of hes6 mRNA expression. This downstream region, which we termed the PT enhancer, possessed several putative binding sites for the T-box and Ets transcription factors that were required for the regulatory activity. Indeed, the T-box transcription factor (Tbx16) and Ets transcription factor (Pea3) bound specifically to the putative binding sites and regulated the enhancer activity in zebrafish embryos. In addition, the 3'UTR of hes6 is required for recapitulation of the endogenous mRNA expression. Furthermore, the PT enhancer with the 3'UTR of hes6 responded to the inhibition of retinoic acid synthesis and fibroblast growth factor signaling in a manner similar to endogenous hes6. The results showed that transcriptional regulation by the T-box and Ets transcription factors, combined with the mRNA stability given by the 3'UTR, is responsible for the unique expression gradient of hes6 mRNA in the posterior PSM of zebrafish embryos.

Cyclic stretch and hypertension increase retinal succinate: potential mechanisms for exacerbation of ocular neovascularization by mechanical stress.

PURPOSE: We investigated succinate metabolism in cells undergoing clinically relevant cyclic stretch and in spontaneously hypertensive rat (SHR) retina. METHODS: We seeded ARPE-19 cells on 6-well BioFlex collagen I-coated, silicone elastomer-bottomed culture plates. Cells then were subjected to pulsatile stretch using a computer-controlled vacuum stretch apparatus. A physiologic stretch frequency of 60 cycles per minute and 5% to 15% prolongation of the elastomer-bottomed plates were used. Succinate concentration was assessed by enzymatic analysis and high-performance liquid chromatography-mass spectrometry. The VEGF was measured using enzyme-linked immunosorbent assays. The 12-week-old male SHRs and weight-matched Wistar-Kyoto (WKY) control rats were treated with or without 100 mg·kg(-1)·day(-1) captopril for 1 week. The vitreous body and retina of each rat were extracted after 1 week of therapy, and the vitreoretinal succinate concentration was measured. RESULTS: Cells exposed to cyclic stretch accumulated intracellular succinate in a time- and magnitude-dependent manner, and also accumulated VEGF protein levels. Moreover, BAPTA/AM, an intracellular calcium chelate reagent, significantly inhibited the stretch-induced succinate increase. After cyclic stretch, levels of intracellular fumarate, a citric acid cycle intermediate, also were significantly increased compared to controls. The BAPTA/AM inhibited this increase. For the in vivo experiments, hypertension increased vitreoretinal succinate and fumarate in SHRs compared to the normotensive WKY controls. When hypertension was reduced using captopril, vitreoretinal succinate returned to baseline levels. CONCLUSIONS: These findings suggest that cyclic stretch and hypertension increased intracellular succinate in cultured retinal pigment epithelial cells and the vitreoretinal succinate of SHRs through a calcium-dependent pathway.

Glaucoma in atomic bomb survivors.

Radiation has been associated with increases in noncancerous diseases. An effect of low-dose radiation on the prevalence of clinically detected glaucoma has not been previously reported. We therefore investigated the prevalence of glaucoma in A-bomb survivors and its possible association with radiation dose. A total of 1,589 people who participated in the clinical examination program for A-bomb survivors at the Radiation Effects Research Foundation (RERF) between October 2006 and September 2008 and who had reconstructed radiation doses, were recruited into this cross-sectional screening study. The prevalence of glaucoma and its dose-response relationship to A-bomb radiation were measured. Each subject underwent an initial screening consisting of an interview and ophthalmological examination. Questionable cases with any indication of ocular disease, including glaucoma, were referred to local hospitals for more comprehensive evaluation. A diagnosis of glaucoma was made based on specific optic disc appearance, perimetric results and other ocular findings. Of 1,589 eligible people, we detected 284 (17.9%) cases of glaucoma overall, including 36 (2.3%) cases of primary open-angle glaucoma with intraocular pressure levels greater than 21 mmHg, 226 (14.2%) cases of normal-tension glaucoma and 25 (1.6%) cases of primary angle-closure glaucoma. Seven glaucoma risk factors were examined as potential confounders but only two needed to be included in the final model. Binary regression using a generalized estimating equation method, with adjustment for gender, age, city, cataract surgery or diabetes mellitus, revealed an odds ratio at 1 Gy of 1.31 (95% confidence interval 1.11-1.53, P = 0.001) in the case of normal-tension glaucoma, but no association for other types of glaucoma. The prevalence of normal-tension glaucoma may increase with A-bomb radiation dose, but uncertainties associated with nonparticipation (59% participation) suggest caution in the interpretation of these results until they are confirmed by other studies.

Succinate increases in the vitreous fluid of patients with active proliferative diabetic retinopathy.

PURPOSE: To examine vitreous succinate levels from proliferative diabetic retinopathy (PDR) patients and ascertain their association with PDR activity. DESIGN: Comparative case series. METHODS: A total of 81 eyes of 72 PDR patients were divided into active PDR (22 eyes), quiescent PDR (21 eyes), and active PDR with intravitreal bevacizumab injection (38 eyes). Twenty epiretinal membrane (ERM) patients (21 eyes) served as controls. RESULTS: Mean vitreous succinate levels were 1.27 µM in ERM and 2.20 µM in PDR, with the differences statistically significant (P = .03). When comparing mean vitreous succinate levels (active PDR: 3.32 µM; quiescent PDR: 1.02 µM; active PDR with intravitreal bevacizumab injection: 1.20 µM), significant differences were found between active and quiescent PDR (P < .01) and between active PDR and active PDR with intravitreal bevacizumab injection (P < .01). Even though succinate levels were low, retinopathy activities were very high in patients with active PDR with intravitreal bevacizumab injection. Mean vitreous vascular endothelial growth factor (VEGF) levels (active PDR: 1696 pg/mL; quiescent PDR: 110 pg/mL; active PDR with intravitreal bevacizumab injection: n.d.) were similar to previous reports. Mean vitreous erythropoietin levels (active PDR: 703 mIU/mL; quiescent PDR: 305 mIU/mL; active PDR with intravitreal bevacizumab injection: 1562 mIU/mL) suggested very high retinopathy activities in patients with active PDR with intravitreal bevacizumab injection. CONCLUSIONS: Succinate, like VEGF, may be an angiogenic factor that is induced by ischemia in PDR. Although succinate is reported to promote VEGF expression, VEGF inhibition decreases succinate. Thus, VEGF, via a positive feedback mechanism, may regulate succinate.

Decreased activities of daily living and associations with bone loss among aged residents in a rural Japanese community: the Miyama Study.

The present study aimed to clarify frequencies of decreased activities of daily living (ADL) and associations with rate of bone loss among inhabitants more than 60 years old in Miyama, a rural community in Japan. A cohort of 1543 inhabitants aged 40-79 years was established according to Miyama resident registrations in 1989. Men (n = 50) and women (n = 50) from each of two age strata between 60 and 79 years (N = 200) were selected from this cohort, and bone mineral density (BMD) of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry in 1990 (initial survey) and again in 1993, 1997, and 2000. Difficulties involving ADL were surveyed at every follow-up study. Of the 200 initial participants, 124 (57 men, 67 women; 62.0%) completed all BMD measurements and answered all items about ADL in the follow-up survey. The following items were investigated as a general indication of changes to ADL: reaching objects on a high shelf or cupboard (reaching); washing and drying the body (washing body); washing hair over a washbasin (washing hair); sitting for 1 h on a hard chair (sitting); raising the torso from a lying position in bed (raising); standing continuously for 30 min (standing); taking socks on and off the feet (taking socks); bending down from a seated position and picking up a small object at the side of the chair (bending); lifting heavy objects (lifting); and running 100 m without stopping (running). Among ADL items, the most frequent difficulties in men involved running (50.0%), followed by raising (30.6%), standing (27.1%), sitting (24.7%), and reaching (16.5%). In women, difficulties involved running (67.0%), followed by lifting (36.3%), standing (33.1%), reaching (30.8%), and sitting (23.6%). To evaluate relationships between decreased ADL and changes in BMD, annual rates of change for BMD at the lumbar spine and femoral neck were compared to changes for each ADL item (2 grade decrease; 1 grade decrease; or no change). Analysis of covariance (ANCOVA) was then performed on decreased ADL and annual bone changes after adjustment for age, concomitant disease (previous fractures, gastrectomy, diabetes mellitus, and renal dialysis at initial survey). In men, annual rates of change in BMD at the femoral neck over 10 years were significantly correlated with decreased abilities in bending (P = 0.046; R2 = 0.10). In women, annual rates of change in BMD at the lumbar spine over 10 years were significantly correlated with decreased abilities in reaching (P = 0.007; R2 = 0.25), and lifting (P = 0.014, R2 = 0.27), and those at the femoral neck were significantly correlated with decreased abilities in lifting (P = 0.001, R2 = 0.33).

Risk factors for knee osteoarthritis in Japanese men: a case-control study.

Risk of knee osteoarthritis (OA) was assessed in a population-based case-control study of Japanese men. The study covered three health districts in Wakayama and Osaka prefectures, Japan. Subjects were male individuals >or=45 years old diagnosed radiographically with knee OA, and who did not display any established causes of secondary OA. Controls selected randomly from the general population were individually matched to cases for age, sex, and residential district. Subjects were interviewed using structured questionnaires to determine medical history, physical activity, socio-economic factors, and occupation. Interviews were obtained from 37 cases and 37 controls. In univariate analysis, heaviest weight in the past and physical work such as factory, construction, agricultural, or fishery work as the principal occupation significantly raised the risk of male knee OA (P<0.05). Odds ratios (OR) were determined using conditional logistic regression analysis mutually adjusted for potential risk factors using the results of univariate analysis. Heaviest weight in the past (OR 6.01, 95% confidence interval (CI) 1.18-30.5, P<0.05), past knee injury (OR 6.25, 95% CI 1.13-34.5, P<0.05), and physical work as the principal occupation (OR 6.20, 95% CI 1.40-27.5, P<0.05) represented independent factors associated with knee OA after controlling for other risk factors. Physical work is associated with knee OA, demonstrating the influence of working activity on the development of OA. The present study suggests that risk factors for knee OA in men resemble those in women.

Risk factors for knee osteoarthritis in Japanese women: heavy weight, previous joint injuries, and occupational activities.

OBJECTIVE: Risk of knee osteoarthritis (OA) associated with constitutional factors, history of joint injuries, and occupational factors was assessed in a case-control study among women in Japan. Results were contrasted with a comparable study in Britain. METHODS: The study covered 3 health districts in Japan. Cases were women aged >/= 45 years old, diagnosed with knee OA by orthopedic physicians utilizing radiography. No cases displayed established causes of secondary OA. Controls selected randomly from the general population were individually matched to each case for age, sex, and residential district. Subjects were interviewed using structured questionnaires to determine medical history, including history of joint injury, physical activity, socioeconomic factors, and occupation. Height and weight were measured. RESULTS: Interviews were obtained from 101 female cases and controls. The highest third of heaviest body weight in the past [high (> 62.0 kg) vs low (< 55 kg) odds ratio = 4.42, 95% confidence interval 1.17-16.64], previous injury to the knee (OR 7.11, 95% CI 2.40-21.09), sedentary work during initial employment (OR 0.35, 95% CI 0.15-0.84), and total working years (OR 1.05, 95% CI 1.01-1.08) represented independent factors associated with knee OA, after controlling for other potential risk factors. CONCLUSION: Heavy weight in the past appears to represent a risk factor for knee OA among women in Japan, as reported in Britain. Constitutional factors may represent important determinants for knee OA, regardless of race. Previous injury to the knee and occupational factors are also associated with knee OA in both Britain and Japan, although characteristic activities for work vary.

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.