The dynamics of bone structure development during pubertal growth

The pubertal growth spurt is a time of rapid changes in bone length, mass and structure, followed by the cessation of longitudinal growth. The two best studied anatomical areas in this respect are the metaphyses and the diaphyses of peripheral long bones. A model is presented here in which the speed of longitudinal growth and the resulting age gradient in metaphyseal bone are key factors in explaining the high incidence of distal radius fractures during puberty. As growth in length accelerates, the age of the bone structural elements at a given distance to the growth plate decreases, leaving less time for cortical thickening through trabecular coalescence. This leads to a discrepancy between stagnant metaphyseal bone strength and increasing mechanical requirements in the case of accidents. In comparison to the metaphysis, diaphyseal bone develops more in line with the increasing mechanical requirements, presumably because the bone formation rates needed for diaphyseal growth in width are only a fraction of the apposition rates in the metaphysis. It remains largely unexplored how local and systemic signals are integrated to achieve site-specific changes in bone structure.     

Injuries causing major loss of scalp

Long hair worn by both sexes in a majority of the rural population of Punjab (India) increases the hazard of descalping injuries. Forty-six cases seen over a period of 10 years are reported. Agricultural machinery accounted for 83 percent of these injuries. Males were most commonly involved (63 percent), and 48 percent of the patients were minors. Nearly all cases reported had at least half the scalp avulsed, 56.5 percent being total scalp avulsions, with bare bone exposed in 48 percent of the total. The method of chiseling the outer portion of the exposed bone down to bleeding points and immediately applying a split-thickness skin graft is presented as the procedure of choice for wound closure. This reduced the average hospitalization period by 49 percent as compared with older methods. Follow-up of 67 percent of patients has revealed a surprising instability of the grafted skin, with an ultimate danger of malignant degeneration.     

Septal fracture in simple nasal bone fracture

SUMMARY: Nasal bone fractures are the most common type of facial fractures. Previous studies have shown that most nasal fractures involve the septum, which can provide an obstacle to the successful reduction of nasal bone fractures. In particular, septal fractures in combination with simple nasal bone fractures are usually unrecognized and untreated at the time of injury. Furthermore, systemized treatment protocols and diagnostic tools for septal fractures in the case of simple nasal bone fracture have not previously been presented. In this study, the clinical findings of septal fractures in cases of simple nasal bone fracture were correlated with symptoms, signs, and computed tomography findings and assessed statistically. The patterns of septal fractures in simple nasal bone fractures were assessed by direct vision via hemitransfixion incision. Of the 52 patients with simple nasal bone fracture who presented over a 3-year period and were included in this study, 10 were female and 42 were male, with an average age of 33.8 years (age range, 18 to 61 years). Fifty of these patients (96.2 percent) showed septal fractures, and septoplasty or submucosal resection was performed on 41 patients (78.8 percent) who manifested severe septal fractures of perioperative septal grade 3 or higher. Closed reduction of the nasal bone fracture only was performed on the remaining 11 patients. Among the signs evident at physical examination, mucosal tearing was found to be statistically significant for septal fracture. Computed tomography was found to be very helpful in diagnosing septal fracture but could not predict its severity accurately (Spearman correlation coefficient between computed tomography septal grading and perioperative septal grading, 33.5 percent). Therefore, computed tomography could not be used as a definitive diagnostic modality for septal fractures in terms of deciding whether septoplasty or submucous resection was needed. It is evident that septal fractures are frequent in simple nasal bone fractures that are not combined with other facial bone fractures. This study confirms that there are differences between radiologic findings and perioperative findings. To reduce the incidence of posttraumatic nasal deformity, meticulous physical examinations with subsequent septoplasty or submucosal resection are needed in the treatment of simple nasal bone fracture.     

Oromandibular reconstruction with the radial-forearm osteocutaneous flap: experience with 60 consecutive cases

One of the more difficult problems in reconstructive surgery of the head and neck is replacement of bone and soft tissue lost because of injury, osteomyelitis, or malignancy. The radial-forearm osteocutaneous flap is an accepted choice for oromandibular reconstruction. This study was undertaken to review one center's experience with 60 consecutive cases of oromandibular reconstruction with the radial-forearm osteocutaneous flap. Records of the 38 men and 22 women (mean age, 60 years; range, 26 to 86 years) were reviewed for tumor location, defect and bone length, flap failure rate, recipient- and donor-site complications, length of surgery, and hospital stay. Cancer resection was the reason for 97 percent of reconstructions; 33 percent of flaps were used to reconstruct a lateral defect of the mandible, 40 percent a lateral-central defect, and 27 percent a lateral-central-lateral defect. Mean skin flap size was 55 cm2 (range, 15 to 117 cm2) and mean bone length, 9.4 cm (range, 5 to 14 cm). The microvascular success rate was 98.3 percent. Complications included fracture of the donor radius (15 percent), nonunion of the mandible (5 percent), and hematoma (8.3 percent). These results are comparable to results reported in the literature with other radial forearm flaps. The free radial osteocutaneous flap is a safe and reliable choice for mandibular reconstruction. It offers sufficient bone to reconstruct large defects and can provide adequate pedicle length for vessel anastomosis to the contralateral side of the neck. The above attributes make the radial forearm osteocutaneous flap one of the "first line" flap choices for oromandibular reconstruction.     

Increasing human tooth length between birth and 5.4 years

Most previous studies of tooth development have used fractional stages of tooth formation to construct growth standards suitable for aging juvenile skeletal material. A simple alternative for determining dental age is to measure tooth length throughout development. In this study, data on tooth length development are presented from 63 individuals of known age at death, between birth and 5.4 years, from an archeological population recovered from the crypt of Christ Church, Spitalfields, London. Isolated developing teeth (304 deciduous, 269 permanent) were measured in millimeters and plotted against individual age. Regression equations to estimate age from a given tooth length, are presented for each deciduous maxillary and mandibular tooth type and for permanent maxillary and mandibular incisors, canines, and first permanent molars. Data on the earliest age of root completion of deciduous teeth and initial mineralization and crown completion of some permanent teeth in this sample are given, as well as the average crown height and total tooth length from a small number of unworn teeth. This method provides an easy, quantitative and objective measure of dental formation appropriate for use by archeologists and anthropologists. © 1993 Wiley-Liss, Inc.     

Percent osteonal bone versus osteon counts: the variable of choice for estimating age at death.

Ahlqvist and Damsten's (1969) modification of the Kerley (1965) method for histological age estimation uses percent osteonal bone, rather than actual osteon counts, in order to eliminate the difficulty of distinguishing between intact and fragmentary osteons. Since their method has been developed for the femur only, and several more recent methods have been proposed that utilize percent osteonal bone, a study was undertaken to ascertain the relative value of percent osteonal bone compared with osteon counts to estimate age at death for the radius, tibia, and fibula. First the question of how much of the cross-section of a bone should be sampled was addressed by comparing the results of regression against age for percent osteonal bone derived from sampling only four fields with those derived from the entire cross-section of the radius. A significant age association was found only when the entire cross-section was sampled. In order to evaluate the relative merit of using either percent osteonal bone, or osteon counts to estimate age, each variable was regressed against age. Significant correlation coefficients were found for all three bones when the independent variable was osteon counts. When percent osteonal bone was employed, a significant correlation was found only for the radius. Stepwise linear regression found osteon counts for the fibula alone to be the best age predictor. Finally, a repeated measures analysis of variance revealed that percent osteonal bone and osteon counts both differ among the three bones within an individual. Based upon these results, osteon counts, rather than percent osteonal bone, should be the variable of choice when developing histological age predicting methods.     

Active life expectancy from annual follow-up data with missing responses

Active life expectancy (ALE) at a given age is defined as the expected remaining years free of disability. In this study, three categories of health status are defined according to the ability to perform activities of daily living independently. Several studies have used increment-decrement life tables to estimate ALE, without error analysis, from only a baseline and one follow-up interview. The present work conducts an individual-level covariate analysis using a three-state Markov chain model for multiple follow-up data. Using a logistic link, the model estimates single-year transition probabilities among states of health, accounting for missing interviews. This approach has the advantages of smoothing subsequent estimates and increased power by using all follow-ups. We compute ALE and total life expectancy from these estimated single-year transition probabilities. Variance estimates are computed using the delta method. Data from the Iowa Established Population for the Epidemiologic Study of the Elderly are used to test the effects of smoking on ALE on all 5-year age groups past 65 years, controlling for sex and education.     

Evaluation of bone height in osseous free flap mandible reconstruction: an indirect measure of bone mass

Osseous free flaps have become the preferred method of mandibular reconstruction after oncologic surgical ablation. To elucidate the long-term effects of free flap mandibular reconstruction on bone mass, maintenance or reduction in bone height over time was used as an indirect measure of preservation or loss in bone mass. Factors potentially influencing bone mass preservation were evaluated; these included site of reconstruction (central, body, ramus), patient age, length of follow-up, adjuvant radiotherapy, and the delayed placement of osseointegrated dental implants. A retrospective analysis of patients undergoing osseous free flap mandible reconstruction for oncologic surgical defects between 1987 and 1995 was performed. Postoperative Panorex examinations were used to evaluate bone height and bony union after osteotomy. Fixation hardware was used as a reference to eliminate magnification as a possible source of error in measurement. There were 48 patients who qualified for this study by having at least 24 months of follow-up. There were 27 male and 21 female patients, with a mean age of 45 years (range, 5 to 75 years). Mandibular defects were anterior (24) and lateral (24). Osseous donor sites included the fibula (35), radius (6), scapula (4), and ilium (3). There were between zero and four segmental osteotomies per patient (excluding the ends of the graft). Nineteen percent of all patients had delayed placement of osseointegrated dental implants. Initial Panorex examinations were taken between 1 and 9 months postoperatively (mean, 2 months). Follow-up Panorex examinations were taken 24 to 104 months postoperatively (mean, 47 months). The bony union rate after osteotomy was 97 percent. Bone height measurements were compared by site and type of reconstruction. The mean loss in fibula height by site of reconstruction was 2 percent in central segments, 7 percent in body segments, and 5 percent in ramus segments. The mean loss in bone height after radial free flap mandible reconstruction was 33 percent in central segments and 37 percent in body segments; ramus segments did not lose height. The central and body segments reconstructed with scapular free flaps did not lose height, but one ramus segment lost 20 percent of height. There was no loss in bone height in mandibular body reconstruction with the ilium free flap. Fibula free flaps did not significantly lose bone height when evaluated with respect to age, follow-up, radiation therapy, or dental implant placement. The retention in bone height demonstrated in this study suggests that bone mass is preserved after osseous free flap mandible reconstruction. The greatest amount of bone loss was seen after multiply osteotomized radial free flaps were used for central mandibular reconstruction. The ability of the fibula free flap to maintain mass over time, coupled with its known advantages, further supports its use as the "work horse" donor site for mandible reconstruction.     

Reconstruction of late craniofacial deformities after irradiation of the head and face during childhood

Little is known about the results of surgical management of late craniofacial abnormalities arising after irradiation of the head and face for treatment of childhood cancers. The clinical records of 10 children (4 males and 6 females) who received 4500 to 6500 rads (mean 5160 rads) of craniofacial radiation between birth and 8 years of age (mean 5 years) and who subsequently had reconstructive surgery were reviewed. Six of the 10 patients received orbital radiation, 3 received maxillary-midfacial radiation, and 1 patient underwent radiation to the frontal bone. Histologic tumor types included retinoblastoma (4), rhabdomyosarcoma (3), Ewing's sarcoma (2), and neurofibrosarcoma (1). In addition to radiation, 7 of the 10 patients underwent surgical resection or debulking of their tumors and 6 received adjuvant chemotherapy. All patients presented from 4 to 20 years after treatment (mean 10 years) with varying, but severe degrees of soft-tissue and bony hypoplasia of the irradiated territories. Onlay bone grafting with soft-tissue reconstruction by a combination of local pedicle flaps and dermal-fat grafts was initially performed in 9 patients, and an occipitoparietal bone-flap switch procedure was done in 1 patient. Late follow-up ranged from 11 months to 7.5 years (mean 34 months). A total of 8 secondary procedures were necessary in 4 of the 10 patients (40 percent). Of these 4 patients, major revisions were performed in 3 and minor adjustments in 1. In addition, 2 patients in whom secondary procedures had not been done would benefit from further reconstruction. Therapy for cancer of the head and face during childhood has profound and ongoing effects on the growth of soft tissue and bone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Food Consumption, Feed Efficiency, Metabolic Rate and Utilization of Glucose in Lines of TRIBOLIUM CASTANEUM Selected for 21-Day Pupa Weight

Growth rate, body composition, cell number, cell size, and the activity of four dehydrogenase enzymes were studied from 10 to 25 days of age in one control (1C) and three lines (3, 9, 10) of Tribolium castaneum that had been subjected to long term selection for large 21-day pupae weight.—Selected lines were two- to three-fold larger in size than the control line throughout development. No major differences in percent of protein were detected among the lines but at any particular age, the selected lines were found to have a higher fat content than the control line. The differences in fat content were closely correlated with development such that all the lines reached very similar levels of percent of fat just prior to pupation. Water content showed an inverse relation to percent of fat.—Selection was observed to have caused major changes in the cellular response to growth. The selected lines had an average of from 17% to 48% larger cells (measured as protein/DNA) and were found to have from 37 to 62% more cells (measured as total DNA) than the control line at all ages from 10 to 19 days of age. In addition, the selected lines had a higher RNA content at all ages studied and higher RNA:DNA ratios at the young ages. In contrast the enzyme activities of ICDH and LDH were 60% lower. The results are interpreted as indicating that a more efficient metabolic machinery had evolved in the rapidly growing selected lines.     

Growth Rate, Body Composition, Cellular Growth and Enzyme Activities in Lines of TRIBOLIUM CASTANEUM Selected for 21-Day Pupa Weight

Growth rate, body composition, cell number, cell size, and the activity of four dehydrogenase enzymes were studied from 10 to 25 days of age in one control (1C) and three lines (3, 9, 10) of Tribolium castaneum that had been subjected to long term selection for large 21-day pupae weight.-Selected lines were two- to three-fold larger in size than the control line throughout development. No major differences in percent of protein were detected among the lines but at any particular age, the selected lines were found to have a higher fat content than the control line. The differences in fat content were closely correlated with development such that all the lines reached very similar levels of percent of fat just prior to pupation. Water content showed an inverse relation to percent of fat.-Selection was observed to have caused major changes in the cellular response to growth. The selected lines had an average of from 17% to 48% larger cells (measured as protein/DNA) and were found to have from 37 to 62% more cells (measured as total DNA) than the control line at all ages from 10 to 19 days of age. In addition, the selected lines had a higher RNA content at all ages studied and higher RNA:DNA ratios at the young ages. In contrast the enzyme activities of ICDH and LDH were 60% lower. The results are interpreted as indicating that a more efficient metabolic machinery had evolved in the rapidly growing selected lines.     

Free tissue coverage of chronic traumatic wounds of the lower leg

Thirty-eight consecutive patients who underwent 42 free flaps for chronic wounds of the lower leg were identified over an 11-year period. All wounds were open for a minimum of 1 month (mean, 40 months; median, 8 months; range, 1 month to 30 years). The average age was 37 years (range, 7 to 68 years), there were 31 male patients and seven female patients, and the average follow-up time was 30 months (range, 12 to 72 months). The original injury was an open fracture in 28 patients, wound dehiscence after open reduction and internal fixation of a closed fracture in nine patients, and a shrapnel wound in one patient. A total of 23 patients had osteomyelitis, which was classified as local (involving less than 50 percent of the bone diameter) in 15 patients and as diffuse (involving greater than 50 percent of the bone diameter or infected nonunion) in eight patients. The wounds were treated with sequential debridement, antibiotics, and flap coverage. Ancillary procedures included antibiotic beads in 18 patients, saucerization in 16, Ilizarov bone transport in three, calcanectomy in two, and fibular resection and ankle fusion in one. Thirty-four of 42 flaps survived, four having undergone a repeat free flap. There were three failures out of 25 flaps (12 percent) among those with a normal angiogram and five failures out of 15 flaps (33 percent) among those with an abnormal angiogram (p > 0.05). The failure rate of those with osteomyelitis was six of 26 (23 percent) versus two of 26 (13 percent) for those without osteomyelitis (p > 0.05). Successful reconstruction (bone healed, patient ambulatory and infection-free) was achieved in 33 of 38 patients (87 percent). The failure of reconstruction for those patients with osteomyelitis was four of 23 (22 percent) versus one of 15 (7 percent) for others (p > 0.05). The failure rate of flaps in patients with diffuse osteomyelitis was three of eight (38 percent) versus two of 30 for others (7 percent, p = 0.053). The presence of diffuse osteomyelitis was associated with a lower rate of successful limb reconstruction. An abnormal angiogram and the presence of osteomyelitis both were associated with a lower rate of successful limb reconstruction, but this was not significant, probably because of the small size of the cohort.     

The childhood component of the ICP model is appropriate for growth analysis of short Israeli children

OBJECTIVE: To determine whether the childhood component of the infancy-childhood-puberty (ICP) model is appropriate for growth analysis of short Israeli children. SUBJECTS AND METHODS: From 204 short, prepubertal children, 2-16 years of age, 1,516 height measurements were analyzed. For each child's measurements, a best-fitted line based on C equation of ICP has been drawn and the distribution of measurement points around that line was calculated. RESULTS: Ninety percent of the measurements were at a distance of no more than +/- 2 cm from the best-fitted ICP line. CONCLUSION: The C component of ICP model can be used as a growth analysis tool for shorter than average, prepubertal, Israeli children, older than 2 years of age.     

The role of estrogen receptor-beta, in the early age-related bone gain and later age-related bone loss in female mice

The molecular and cellular mechanism of estrogen action in skeletal tissue remains unclear. The purpose of this study was to understand the role of estrogen receptor-beta, (ERbeta) on cortical and cancellous bone during growth and aging by comparing the bone phenotype of 6- and 13-month-old female mice with or without ERbeta. Groups of 11-14 wild-type (WT) controls and ERbeta knockout (BERKO) female mice were necropsied at 6 and 13 months of age. At both ages, BERKO mice did not differ significantly from WT controls in uterine weight and uterine epithelial thickness, indicating that ERbeta does not regulate the growth of uterine tissue. Femoral length increased significantly by 5.5% at 6 months of age in BERKO mice compared with WT controls. At 6 months of age, peripheral quantitative computerized tomography (pQCT) analysis of the distal femoral metaphysis (DFM) and femoral shafts showed that BERKO mice had significantly higher cortical bone content and periosteal circumference as compared with WT controls at both sites. In contrast to the findings in cortical bone, at 6 months of age, there was no difference between BERKO and WT mice in trabecular density, trabecular bone volume (TBV), or formation and resorption indices at the DFM. In 13-month-old WT mice, TBV (-41%), trabecular density (-27%) and cortical thickness decreased significantly. while marrow cavity and endocortical circumference increased significantly compared with 6-month-old WT mice. These age-related decreases in cancellous and endocortical bone did not occur in BERKO mice. At 13 months of age, BERKO mice had significantly higher total, trabecular and cortical bone, while having significantly lower bone resorption, bone formation and bone turnover in DFM compared with WT mice. These results indicate that deleting ERbeta protected against age-related bone loss in both the cancellous and endocortical compartments by decreasing bone resorption and bone turnover in aged female mice. These data demonstrate that in female mice, ERbeta plays a role in inhibiting periosteal bone formation, longitudinal and radial bone growth during the growth period, while it plays a role in stimulating bone resorption, bone turnover and bone loss on cancellous and endocortical bone surfaces during the aging process.     

The frequency of appearance of transverse lines in the tibia in relation to childhood illnesses

The hypothesis that transverse lines of increased density in growing bones are caused by illnesses and other traumas of childhood was investigated using tibial x-rays and medical records of 107 boys and 94 girls in the Fels longitudinal series. There is not a one to one relationship between even severe illnesses and line formation. The frequency of appearance of lines at each age interval, one month through fourteen years, was calculated for both sexes separately and combined, in order to show periods of maximum formation. That transverse lines are “growth arrest” lines which cause ultimate growth retardation was discounted since no significant difference in finally attained adult stature was noted between heavily and lightly lined subjects.     

Development and growth of long bones in European water frogs (Amphibia: Anura: Ranidae), with remarks on age determination

Differentiation and development of long bones were studied in European water frogs: Rana lessonae, R. ridibunda, and R. esculenta. The study included premetamorphic larvae (Gosner Stage 40) to frogs that were 5 years old. Femora, metatarsal bones, and proximal phalanges of the hindlimb exhibit the same pattern of periosteal bone differentiation and the same pattern of growth. Longitudinal and radial growth of these bones was studied by examination of the diaphyses and epiphyses, particularly where the edge of periosteal bone is inserted into the epiphysis. The periosteum seems to be responsible for both longitudinal and radial growth. Investigation of the formation, length, and arrangement of lines of arrested growth reveals that the first line is present only in the middle 25-35% of the length of the diaphysis of an adult bone; therefore, only the central portion of the diaphysis should be used for age estimation in skeletochronological studies. Comparison of the shapes and histological structures of epiphyses in the femur, metatarsal bones, and phalanges revealed that epiphyseal cartilages are composed of an inner and outer part. The inner metaphyseal cartilage has distinct zones and plugs the end of the periosteal bone cylinder; its role in longitudinal growth is questioned. The outer epiphyseal cartilage is composed of articular cartilages proper, in addition to lateral articular cartilages. Differences in the symmetry of the lateral articular cartilages of distal epiphyses of the femur and toes may reflect adaptations to different kinds of movements at the knee and in the foot.     

Osteoporosis: the current status of mesenchymal stem cell-based therapy

Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves a balance between bone resorption and bone formation during early adulthood. In osteoporosis, this process becomes imbalanced, resulting in gradual losses of bone mass and density due to enhanced bone resorption and/or inadequate bone formation. Several growth factors underlying age-related osteoporosis and their signaling pathways have been identified, such as osteoprotegerin (OPG)/receptor activator of nuclear factor B (RANK)/RANK ligand (RANKL), bone morphogenetic protein (BMP), wingless-type MMTV integration site family (Wnt) proteins and signaling through parathyroid hormone receptors. In addition, the pathogenesis of osteoporosis has been connected to genetics. The current treatment of osteoporosis predominantly consists of antiresorptive and anabolic agents; however, the serious adverse effects of using these drugs are of concern. Cell-based replacement therapy via the use of mesenchymal stem cells (MSCs) may become one of the strategies for osteoporosis treatment in the future.     

Shell growth and chamber formation of aquarium-reared Nautilus pompilius (Mollusca, Cephalopoda) by X-ray analysis

Observations on the growth rate of aquarium maintained Nautilus pompilius in different developmental stages, i.e. juveniles (shell length about 8.75 cm), late juveniles (approximately 10 cm), and early adolescent (approximately 13.5 cm), indicate that this species is fully grown at an age of 7.3-8 years. The age calculations are based on two different computations: (1) the measurement of the increase of the shell length per day and (2) the formation of new septa in time intervals of 150+/-5 days, as demonstrated by X-ray analyses. After N. pompilius hatches, its shell grows about 139 mm to reach full growth and approximately 28 septa are formed. With an increase of the shell length of 0.052 mm per day, it takes about 2,673 days (7.3 years) to reach maturity. Provided that the process of chamber formation follows an exponential function, these computations result in approximately 2,925 days (8 years) to reach full maturity. Supposing that N. pompilius may live for several years after onset of maturity like Nautilus belauensis, the total life span for this species may exceed 11-12 years.     

Hypercalcaemia in relapsed medulloblastoma 8 years post-diagnosis; evidence to support PTHrP production by medulloblastoma cells

BACKGROUND: A 19-year-old male presented with symptomatic hypercalcaemia as the first manifestation of relapsed metastatic medulloblastoma. Management at the time of the initial presentation 8 years earlier was with surgical excision and craniospinal radiotherapy. His biochemistry at the time of relapse and studies of medulloblastoma cell lines provide an insight into the pathogenesis of his hypercalcaemia. METHODS: Parathyroid hormone-related protein (PTHrP) was measured by immunoradiometric assay in blood, and in conditioned and control media from three medulloblastoma cell lines following 72 h growth. RESULTS: The histology at initial presentation (11 years of age) and at the time of relapse (with bone marrow infiltration and widespread bony metastases) demonstrated medulloblastoma. Ionised calcium concentrations at relapse were 2.89 mmol/l and serum PTHrP levels were increased at the same time (2.7 pmol/l; normal range: 0.7-1.8 pmol/l). There was evidence of PTHrP production by one cell line (MHH-MED-8A) while results for both other lines tested were below the limit of detection. CONCLUSIONS: Relapse 8 years after diagnosis is unusual in medulloblastoma and for this relapse to manifest as hypercalcaemia is also very uncommon. Our investigations suggest that the clinical picture was a reflection of PTHrP production by medulloblastoma cells.