Influence of Severity on Aesthetic Outcomes of Unilateral Cleft Lip Repair in 1,823 Patients.

BACKGROUND: Although efforts to improve access to care for patients with cleft lip in the developing world have grown tremendously, there is a dearth of data regarding aesthetic outcomes after cleft lip repairs in this setting. Defining severity-outcome relationships has the potential to improve efficiency of care delivery in resource-limited settings, and to improve overall results. In this study, we investigate the relationship between initial cleft lip severity and early aesthetic outcomes following surgical repair of primary unilateral cleft lip. METHODS: Using previously validated tools to assess unilateral cleft lip severity and aesthetic outcome after repair, we evaluated 1,823 consecutive patients who underwent primary unilateral cleft lip/nose (UCL/N) repair. Three separate evaluators scored each case for a total of 5,469 total independent evaluations. RESULTS: Our results show that with increasing severity of UCL/N deformity, there is a corresponding decrease in early aesthetic outcome scores. Using our results, we established normative early aesthetic outcomes following repair for each severity grade of UCL/N deformity. CONCLUSIONS: In conclusion, this study has achieved a standardized, timely, and cost-effective evaluation of 1,823 surgical cases of primary UCL/N repair. This data set provides a normal distribution of aesthetic results according to initial cleft severity and defines a standard of "expected" aesthetic results after primary UCL/N repair. Our results also show a clear correlation between initial severity and immediate aesthetic result after surgery, though we also show that excellent results are possible regardless of initial cleft severity.

Evaluation of Facial Anthropometry Using Three-Dimensional Photogrammetry and Direct Measuring Techniques.

In this study, 14 standard facial distances on 10 adult volunteers were measured directly with a caliper and indirectly on two-dimensional images using the 3dMDtrio system. Two raters performed the measurements with at least 1 week between rating sessions. The intra- and inter-rater reliabilities and agreement of the measurements were calculated using intra-class correlation coefficient (ICC), mean absolute difference (MAD), and Bland-Altman plots with limits of agreement (LOA). The 2 raters had an average discrepancy (MAD) of 1.6 mm when their digital measurements were compared to their direct measurements. The reliability of the digital and direct methods varied greatly depending on which of the 14 anthropometric distances that was being assessed. Only 6 digitally and 5 directly measured anthropometric distances showed both an ICC >0.75 and a MAD <1 mm, in the intra-rater as well as the inter-rater measurements. The Bland-Altman plots and LOA displayed the same pattern. In summary, the digital and direct methods were generally compatible in terms of reliability and agreement. However, the reliability and agreement between the 14 anthropometric measurements varied considerably, indicating that poor landmark identification is the main limitation to both modern and traditional measuring techniques in the face. Consequently, some anthropometric landmarks warrant further definition or prior anthropometric training by the evaluators. The authors also recommend that the MADs and LOAs provided in this report are put into relation to the facial distance that is being evaluated and its clinical context.

Speech in 5-Year-Olds With Cleft Palate With or Without Cleft Lip Treated With Primary Palatal Surgery With Muscle Reconstruction According to Sommerlad.

OBJECTIVE: To evaluate speech in 5-year-olds with cleft palate with or without cleft lip (CP±L) treated with primary palatal surgery in 1 stage with muscle reconstruction according to Sommerlad at about 12 months of age. DESIGN: Retrospective study. SETTING: Primary care university hospital. PARTICIPANTS: Eight 5-year-olds with cleft soft palate (SP), 22 with cleft soft/hard palate (SHP), 33 with unilateral cleft lip and palate, and 17 with bilateral CLP (BCLP). MAIN OUTCOME MEASURES: Percent oral consonants correct (POCC), percent consonants correct adjusted for age (PCC-A), percent oral errors, percent nonoral errors, and variables related to velopharyngeal function were analyzed from assessments of audio recordings by 3 independent speech-language pathologists. RESULTS: The median POCC was 75.4% (range: 22.7%-98.9%), median PCC-A 96.9% (range: 36.9%-100%), median percent oral errors 3.4% (range: 0%-40.7%), and median percent nonoral errors 0% (range: 0%-20%), with significantly poorer results in children with more extensive clefts. The SP group had significantly less occurrence of audible nasal air leakage than the SHP and the BCLP groups. Before age 5 years, 1.3% of the children underwent fistula surgery and 6.3% secondary speech improving surgery. At age 5 years, 15% of the total group was perceived as having incompetent velopharyngeal function. CONCLUSIONS: Speech was poorer in many children with more extensive clefts. Children with CP±L had poorer speech compared to normative data of peers without CP±L, but the results indicated relatively good speech compared to speech of children with CP±L in previous studies.

Improved Early Cleft Lip and Palate Complications at a Surgery Specialty Center in the Developing World.

OBJECTIVE: To evaluate complication rates following cleft lip and cleft palate repairs during the transition from mission-based care to center-based care in a developing region. PATIENTS AND DESIGN: We performed a retrospective review of 3419 patients who underwent cleft lip repair and 1728 patients who underwent cleft palate repair in Guwahati, India between December 2010 and February 2014. Of those who underwent cleft lip repair, 654 were treated during a surgical mission and 2765 were treated at a permanent center. Of those who underwent cleft palate repair, 236 were treated during a surgical mission and 1491 were treated at a permanent center. SETTING: Two large surgical missions to Guwahati, India, and the Guwahati Comprehensive Cleft Care Center (GCCCC) in Assam, India. MAIN OUTCOME MEASURE: Overall complication rates following cleft lip and cleft palate repair. RESULTS: Overall complication rates following cleft lip repair were 13.2% for the first mission, 6.7% for the second mission, and 4.0% at GCCCC. Overall complication rates following cleft palate repair were 28.0% for the first mission, 30.0% for the second mission, and 15.8% at GCCCC. Complication rates following cleft palate repair by the subset of surgeons permanently based at GCCCC (7.2%) were lower than visiting surgeons ( P < .05). CONCLUSIONS: Our findings support the notion that transitioning from a mission-based model to a permanent facility-based model of cleft care delivery in the developing world can lead to decreased complication rates.

Validation of a Unilateral Cleft Lip Surgical Outcomes Evaluation Scale for Surgeons and Laypersons.

BACKGROUND: A standardized evaluation tool is needed for the assessment of surgical outcomes in cleft lip surgery. Current scales for evaluating unilateral cleft lip/nose (UCL/N) aesthetic outcomes are limited in their reliability, ease of use, and application. The Unilateral Cleft Lip Surgical Outcomes Evaluation (UCL SOE) scale measures symmetry of 4 components and sums these for a total score. The purpose of this study was to validate the SOE as a reliable tool for use by both surgeons and laypersons. METHODS: Twenty participants (9 surgeons and 12 laypeople) used the SOE to evaluate 25 sets of randomly selected presurgical and postsurgical standardized photographs of UCL/N patients. Interrater reliability for surgeon and laypeople was determined using an intraclass correlation coefficient (ICC). RESULTS: Individual surgeons and laypeople both reached an ICC in the "fair to good" range (ICC = 0.42 and 0.59, respectively). Averaging 2 evaluators in the surgeon group improved the ICC to 0.58 and in the laypeople group to 0.74, respectively. Averaging 3 evaluators increased the ICC for surgeons to the "good" range (ICC = 0.71) and the ICC for laypeople to the "very good" range (ICC = 0.82). CONCLUSIONS: Surgeon and layperson raters can reliably use the SOE to assess the aesthetics results after surgical repair of UCL/N, and improved reliability and reproducibility is achieved by averaging the scores of multiple reviewers.

Validation of the Unilateral Cleft Lip Severity Index for Surgeons and Laypersons.

BACKGROUND: Severity of the primary unilateral cleft lip/nose deformity (UCL/N) is postulated to play a key role in postoperative complications, aesthetic result, and need for secondary surgery. There is no validated and widely accepted classification scheme of initial cleft severity. The purpose of this study was to validate the Unilateral Cleft Lip Cleft Severity Index as a reliable tool for evaluating presurgical UCL/N deformity by both surgeons and laypersons. METHODS: Twenty-five participants (10 surgeons and 15 laypeople) evaluated 25 sets of randomly selected presurgical standardized photographs of UCL/N patients. Each participant rated patients on a scale of 1-4 using the Cleft Severity Index. Interrater reliability for surgeons, laypersons, and all participants was determined using an intraclass correlation coefficient. Histograms and regression analysis were performed to compare average ratings between groups. RESULTS: Interrater reliability for all groups was classified as "very good" determined by intraclass correlation coefficients of 0.837 (laymen), 0.885 (surgeons), and 0.848 (all participants). These results indicate that there was a high degree of interrater across all 3 groups and that both surgeons and laypersons can reliability rate cleft severity using the Cleft Severity Index. CONCLUSIONS: This study validates the use of the Cleft Severity Index by both surgeons and laypersons as a reliable tool for evaluating the degree of presurgical severity of patients with UCL/N. The Unilateral Cleft Lip Cleft Severity Index can thus serve as a reproducible and reliable grading system for primary UCL/N deformity and to categorize patients for future outcomes studies.

An analysis of complications in secondary bone grafting in patients with unilateral complete cleft lip and palate.

AIM: The aim of this investigation was to assess the outcome of secondary alveolar bone grafts 6 months after the procedure and examine the possible influence of patient sex, age at surgery, cleft width, and dehiscence of mucosa and sequestered bone at 2 weeks. METHODS: Thirty-nine consecutive patients with unilateral complete cleft lip and palate were reconstructed with secondary alveolar bone grafting. Age at surgery ranged from 7.3-12.5 years (mean = 8.6). Cleft width varied between 2.2-14 mm (mean = 7.3). Bone was harvested either from the iliac crest or from the chin. Two-dimensional dental radiographs of the cleft area were taken before and 6 months after surgery. RESULTS: Two weeks after surgery, 10 patients had minor dehiscence of the sutured gingival tissues and five had bone sequesters. However, only one of the treatments turned out to be unsuccessful with a Bergland index of IV. Twenty-nine patients had an initial uneventful course; but, at a follow-up 6 months later, two patients had a Bergland index of III and four a Bergland index of IV. In three of these cases, there were circumstances that could have contributed to the lack of success; but, in the remaining three, no such circumstances could be identified. CONCLUSION: The success rate of secondary bone grafting is high, and initial wound healing problems do not necessarily lead to a failed reconstruction. Failure may be related to factors such as exposed tooth enamel during an operation, postoperative infection, and poor compliance. Still, failed operations occur without any obvious causes.

Surgical Complications in 1408 Primary Cleft Palate Repairs Operated at a Single Center in Guwahati, Assam, India.

OBJECTIVE: To analyze surgical complications after primary cleft palate repair in a setting with limited resources. PATIENTS AND DESIGN: A total of 1608 consecutive cleft palate repairs with 1408 follow-ups, operated upon between 2011 and 2013, were reviewed retrospectively through medical records. Patients were 10 months to 50 years old at the time of surgery, with a median age of 9 years. SETTING: Guwahati Comprehensive Cleft Care Center, Guwahati, India. INTERVENTION: Primary cleft palate repair. MAIN OUTCOME MEASURES: Postoperative complications in terms of necrosis, dehiscence, fistula, infection, and "hanging palate" were assessed, as was perioperative bleeding. Logistic regression was used with complication (yes/no) as the binary dependent variable and with age, cleft type, and surgeon (visiting/long-term) as covariates. RESULTS: The overall incidence of postoperative complications was 16.9% with a fistula rate of 13.6%. The incidence of perioperative bleeding was 1.8%. Logistic regression analysis identified cleft severity (P ≤ .001) and visiting surgeon (P ≤ .01) as factors related to the incidence of postoperative complications. Age at surgery was related to both the incidence of postoperative complications (P ≤ .001) and perioperative bleeding (P < .05). CONCLUSION: Due to increased risks of surgical complications, older patients with complete clefts should only be operated upon after careful consideration. In addition, these patients should be assigned to surgeons experienced with this cleft type.

Role of Postoperative Antimicrobials in Cleft Palate Surgery: Prospective, Double-Blind, Randomized, Placebo-Controlled Clinical Study in India.

BACKGROUND: The purpose of this study was to determine whether administration of postoperative antibiotics affects the incidence of complications after primary cleft palate repair in a developing area. METHODS: This study was a prospective, double-blind, randomized, placebo-controlled trial composed of 518 consecutive patients who underwent primary cleft palate repair at a single institution. Patients were aged 1 to 43 years at the time of surgery (median, 9 years). The patients were divided randomly into two groups. One group received a 5-day regimen of oral amoxicillin (50 mg/kg/day) postoperatively and the other group received placebo medication. Both groups received a single dose of cefuroxime (30 mg/kg) before incision. Patients and providers were blinded to the randomization. Patients were followed postoperatively for early complications (infection and wound breakdown) and for late complications (palatal fistulas). RESULTS: The incidence of early complications was 13.8 percent among the patients in the placebo group and 8.7 percent among the patients in the antibiotic group (p = 0.175). Fistulas were noted in 17.1 percent in the placebo group and in 10.7 percent in the antibiotic group (p = 0.085). Logistic regression analysis identified visiting surgeons as the only covariate related to early complications (OR, 3.71; p < 0.001). However, the use of placebo (OR, 2.09; p = 0.037), female sex (OR, 2.04; p = 0.047), and Veau III and IV (OR, 3.31; p = 0.004) were observed as factors associated with the incidence of fistulas. CONCLUSION: The authors' results indicate that postoperative antibiotic prophylaxis can reduce the incidence of fistulas after primary cleft palate repair in a developing area.

Limited Chances of Speech Improvement After Late Cleft Palate Repair.

Late primary palatal repair is a common phenomenon, and many patients across the world will be operated on at a far later age than is suggested for normal speech development. Nevertheless, little is known about the speech outcomes after these procedures and conflicting results exist among the few studies performed. In this study, blinded preoperative and postoperative speech recordings from 31 patients operated on at Guwahati Comprehensive Cleft Care Center in Assam, India, older than 7 years were evaluated. Six non-Indian speech and language pathologists evaluated hypernasal resonance and articulation, and 4 local laymen evaluated the speech intelligibility/acceptability of the samples. In 25 of 31 cases, the evaluators could not detect any speech improvement in the postoperative recordings. A clear trend of postoperative improvement was only found in 6 of the 31 patients. Among these 6 patients, lesser clefts were overrepresented. Our findings together with previous studies suggest that late palate repairs have the potential to improve speech, but the probability for improvement and degree of improvement is low, especially in older adolescents and adults with complete clefts.

Speech and Speech-Related Quality of Life After Late Palate Repair: A Patient's Perspective.

Many patients with cleft palate deformities worldwide receive treatment at a later age than is recommended for normal speech to develop. The outcomes after late palate repairs in terms of speech and quality of life (QOL) still remain largely unstudied. In the current study, questionnaires were used to assess the patients' perception of speech and QOL before and after primary palate repair. All of the patients were operated at a cleft center in northeast India and had a cleft palate with a normal lip or with a cleft lip that had been previously repaired. A total of 134 patients (7-35 years) were interviewed preoperatively and 46 patients (7-32 years) were assessed in the postoperative survey. The survey showed that scores based on the speech handicap index, concerning speech and speech-related QOL, did not improve postoperatively. In fact, the questionnaires indicated that the speech became more unpredictable (P < 0.01) and that nasal regurgitation became worse (P < 0.01) for some patients after surgery. A total of 78% of the patients were still satisfied with the surgery and all of the patients reported that their self-confidence had improved after the operation. Thus, the majority of interviewed patients who underwent late primary palate repair were satisfied with the surgery. At the same time, speech and speech-related QOL did not improve according to the speech handicap index-based survey. Speech predictability may even become worse and nasal regurgitation may increase after late palate repair, according to these results.

The efficacy of vomer flap for closure of hard palate during primary lip repair.

BACKGROUND AND AIM: This study presents the institutional experience of the use of vomer flap for early closure of hard palate during unilateral complete cleft-lip repair. The purpose of this study was to determine the survival rate of the vomer flap and to investigate its effect on the subsequent palatoplasty. PATIENTS AND METHODS: This retrospective analysis includes 101 non-syndromic patients with complete unilateral cleft lip who received a vomer flap for the closure of the hard palate during cleft-lip repair. Patients were aged 6 months to 28 years (median 1 year). Success rates of the vomer flaps were assessed clinically and through pre-operative photographs taken at the time of subsequent palate repair. Ninety-two patients returned for second-stage palate repair, and 74 patients with adequate post-operative follow-up information were statistically analysed. RESULTS: Of the 101 patients who were operated with primary lip repair and simultaneous vomer flap, only 54 (52.4%) vomer flaps healed completely. Out of 92 patients who returned for subsequent palatoplasty, 71 (77.2%) were operated with the two-flap technique, and 19 (20.7%) received von Langenbeck repairs. Seven (9.1%) patients had a surgical complication. The failure of previous vomer repair and von Langenbeck surgical technique were identified as factors associated with post-operative complications. CONCLUSIONS: We conclude that failed vomer flaps increased the risks of complications in the subsequent palate repair. Furthermore, efforts to use von Langenbeck technique rather than the two-flap technique also resulted in increased surgical complications. As a result, we have abandoned the use of the vomer flap with primary lip repair.

Subjective outcomes after treatment for velopharyngeal dysfunction.

BACKGROUND: Velopharyngeal dysfunction (VPD) can have various causes and may be a significant disability for the affected patient. Treatment options include surgery and speech therapy, but the success rates are often inconsistent. METHODS: In this study, self-assessment questionnaires were sent out to 222 Swedish patients with VPD. The questionnaire included questions about satisfaction with speech, perceived speech quality, perceived improvement from VPD-surgery, and/or speech therapy. Out of 117 (52.7%) respondents, 114 (51.4%) patients were included in the study. The participants were 7-71 years of age (median = 14 years), diagnosed with cleft palate, neurological/developmental delay, congenital hypernasality, or acquired VPD. All patients had previously undergone videofluoroscopy, and 61.4% had undergone VPD-surgery. RESULTS: Seventy-one per cent of the patients perceived their speech to be normal or slightly deviant, but only 55% were satisfied with their speech. Sixty per cent of the operated on patients felt that the treatment had improved their speech much or very much, 10% thought that they had moderate improvement, and 30% stated that they had no or little improvement. Out of the patients that had received speech therapy, 41% felt that the treatment had improved their speech much or very much, 21% thought that they had moderate improvement, and 33% stated that they had no or little improvement. CONCLUSION: In conclusion, most patients with VPD in this study who underwent evaluation and treatment felt that surgery and speech therapy had improved their speech, but only about half of them were in the end satisfied with the quality of their speech.

Early Surgical Complications After Primary Cleft Lip Repair: A Report of 3108 Consecutive Cases.

OBJECTIVE: To analyze short term surgical complications after primary cleft lip repair. PATIENTS AND DESIGN: A total of 3108 consecutive lip repairs with 2062 follow-ups were reviewed retrospectively through medical records. Patients were aged 3 months to 75 years at the time of surgery, with a median of 7 years. SETTING: Guwahati Comprehensive Cleft Care Center, Assam, India. INTERVENTION: Primary cleft lip repair. MAIN OUTCOME MEASURES: Documented complications in terms of dehiscence, necrosis, infection, and suture granuloma were compiled. Logistic regression was used with dehiscence (yes/no) or infection (yes/no) as binary dependant variables. Age, cleft type, and surgeon (visiting/long term) were used as covariates. RESULTS: Among the 2062 patients who returned for early follow-up, 90 (4.4%) had one or more complications. Dehiscence (3.2%) and infection (1.1%) were the most common types of complication. Visiting surgeon, complete cleft, and bilateral cleft were significantly associated with wound dehiscence, and complete cleft was associated with wound infection according to the logistic regression analysis. Of patients with bilateral complete clefts, 6.9% suffered from some degree of wound dehiscence. CONCLUSION: In a setting where presurgical molding is unavailable and patients present at all ages, lip wound dehiscence is a relatively common complication in patients with bilateral complete clefts. The risk of dehiscence, however, is reduced when these cases are assigned to surgeons with experience with these types of clefts. We also found that the incidence of wound infection can be kept relatively low, even without the use of postoperative antibiotics.

Lessons learned from two consecutive cleft lip and palate missions and the impact of patient education.

Two consecutive cleft missions were conducted in Guwahati, northeastern India in December 2010 and January 2011. In the later mission, a standardized patient education program for postoperative care was introduced. The objective of this study was to retrospectively evaluate the impact of the patient education program on cleft lip complications in terms of wound infection and dehiscence. Two hundred ninety-eight cleft lip repairs were performed in the first mission and 220 (74%) returned for early follow-up. In the second mission, 356 patients were operated on and 252 (71%) returned for follow-up. From the first mission, 8 patients (3.7%) were diagnosed with lip wound infection and 21 patients (9.6%) with lip dehiscence. After the second mission, only 1 patient (0.4%) returned with a wound infection and 16 (6.4%) were diagnosed with dehiscence.Using binary logistic regression including age, cleft type, postoperative antibiotics, surgeon, and patient education program as covariates, the patient education program stood out as the only variable with a statistically significant impact on the incidence of postoperative wound infections. Even though the incidence of lip dehiscence was reduced by one third when the patient education program was utilized, our regression model singled out the surgeons as the only factor significantly related to this type of complication. Moreover, no benefits of postoperative antibiotic prophylaxis were found. Further analysis of the data also implied that the use of tissue adhesive as a compliment to sutures does not reduce the risk of dehiscence.

Neonatal scalp haematoma and necrosis.

Birth trauma after prolonged deliveries and instrument-assisted extractions can result in skin lesions and reduced viability of the scalp. In these instances, scalp swellings and haematomas are often also seen. The classification and inter-relationship between these conditions might not, however, always be clear. This report describes three cases of neonates with scalp swellings and necrosis. Nomenclature, underlying causes, work up, treatment options, and outcomes are presented and discussed. The first case consisted of a newborn with a subgaleal haematoma and occipital pressure necrosis that healed by secondary intention. In the second case, an infected scalp haematoma led to scarring and alopecia that required secondary reconstruction with tissue expansion. The third neonate suffered from a subgaleal haematoma and a scalp lesion that required split skin grafting and secondary reconstruction with tissue expansion.

A review of the tensor veli palatine function and its relevance to palatoplasty.

Abstract The main purpose of palatoplasty is to establish normal speech and deglutition. To enhance the chance of successful palatal repair, as well as optimal velopharyngeal competence, the anatomy of the palate has to be thoroughly understood. While carrying out the repair, some surgeons prefer to cut the tensor veli palatini (TVP) tendon, others perform a tenopexy or fracture the hamulus around which the tendon passes, to facilitate mobilisation of palatal tissue. However, the exact anatomy and function of the TVP is still controversial and severing the tendon or its path could be of potential harm. A review of the literature was conducted to summarise the current knowledge of the TVP and its relevance to palatoplasty. It was found that there is sufficient evidence that the TVP plays an important part in velar tautening and Eustachian tube opening, under normal circumstances. TVP's role in the cleft patient population is, however, less certain. Whether or not TVP tenotomy or dislocation reduces ET function further in these patients is also unclear. There is, however, little or no evidence of reduced middle ear effusions if such actions are avoided, at least not in children younger than 3 years of age.

Vascular endothelial growth factor inhibits bone morphogenetic protein 2 expression in rat mesenchymal stem cells.

INTRODUCTION: While several studies report that bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) can act synergistically to improve bone tissue engineering, others suggest that VEGF inhibits osteogenesis. The purpose of these experiments was therefore to evaluate the effect of dual transfection of these growth factors and potential mechanisms of interaction on gene expression and osteogenesis in vitro and in vivo. METHODS: Marrow-derived mesenchymal stem cells (MSCs) were exposed to recombinant VEGF protein or transfected with adenoviruses encoding BMP2, VEGF, or LacZ in a variety of ratios. Alterations in gene and protein expression in vitro as well as bone formation in vivo were assessed. RESULTS: MSC exposure to AdV-VEGF or recombinant VEGF inhibited BMP2 mRNA expression, protein production, and MSC differentiation. Coculture experiments revealed that BMP2 suppression occurs through both an autocrine and a paracrine mechanism, occurring at the transcriptional level. Compared to controls, cotransfection of VEGF and BMP2 transgenes prevented ectopic bone formation in vivo. CONCLUSION: VEGF is a potent inhibitor of BMP2 expression in MSCs, and supplementation or overexpression of VEGF inhibits osteogenesis in vitro and ectopic bone formation in vivo. Strategies to utilize MSCs in bone tissue engineering therefore require careful optimization and precise delivery of growth factors for maximal bone formation.

Radioprotection of osteoblasts by a fractionated dose regimen and amifostine.

BACKGROUND: Radioprotective modalities such as dose fractionation and pharmacologic agents such as amifostine have been used to protect bone and other types of normal tissue from the damaging effects of ionizing radiation without significantly impacting tumor kill. To better understand the cellular mechanism of radioprotection of osseous tissue, the authors sought to determine the effect of dose fractionation and amifostine on isolated osteoblasts. METHODS: Isolated primary rat calvarial osteoblasts were exposed to single or fractionated doses of ionizing radiation both with and without amifostine pretreatment. Endpoints included cell growth (n = 4), vascular endothelial growth factor production as measured by enzyme-linked immunosorbent assay (n = 3), and early osteodifferentiation as measured by a quantitative alkaline phosphatase assay (n = 3). RESULTS: Both dose fractionation and amifostine protect osteoblasts from the growth inhibitory effects of ionizing radiation. Fractionation but not amifostine was protective for hypoxia-induced vascular endothelial growth factor production (used as a surrogate marker of normal osteoblast function). Neither fractionation nor amifostine could prevent the inhibitory effect of ionizing radiation on normal osteoblast osteodifferentiation as measured by alkaline phosphatase production. CONCLUSIONS: Both dose fractionation and amifostine have valid roles as radioprotectants for osteoblasts and can act in an additive fashion. Radioprotection of cell growth and viability does not necessarily correlate with preservation of normal cellular function. Combination protocols involving dose fractionation and amifostine may be effective in radioprotection of osteoblasts and normal osseous tissue.