Effects of long-term treatment with loop diuretics on bone mineral density, calcitropic hormones and bone turnover.

BACKGROUND: Loop diuretics (LD) are widely used in the treatment of cardiovascular diseases and disorders with fluid accumulation. LD are known to increase renal calcium losses and may thereby affect calcium homeostasis and bone metabolism. OBJECTIVE: We studied to what extent long-term treatment with LD affects calcium homeostasis and bone metabolism. DESIGN AND SUBJECTS: In a cross-sectional design we compared 140 postmenopausal women treated with a LD for more than 2 years with 140 age-matched women not in diuretic therapy. RESULTS: Treatment with LD was associated with significantly increased urinary calcium, plasma parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D levels. Per 40 mg day(-1) of furosemide, urinary calcium was increased by 17% (P < 0.05) and plasma PTH levels were increased by 28% (P = 0.04). Users of LD had a 17% higher body weight (P < 0.001) compared with nonusers. This was due to a 32% higher fat mass (P < 0.001) and a 6% higher lean tissue mass (P < 0.001). Moreover, users of LD had a higher bone mineral density (BMD) at the spine (+7.5%, P < 0.001), hip (+4.8%, P = 0.004), forearm (+3.7%, P = 0.01) and whole body (+2.5%, P = 0.06). However, after adjustment for body weight differences, BMD did not differ between groups. Nevertheless, duration of LD treatment was positively associated with BMD at the spine (P = 0.03) and whole body (P < 0.05). BMD at the spine increases by 0.3% per 1 year of treatment. CONCLUSIONS: The increased renal calcium losses in users of LD are compensated for by a PTH-dependent increase in 1,25(OH)(2)D levels. Thereby calcium balance remains neutral without major effects on bone metabolism.

Healing of 400 intra-alveolar root fractures. 1. Effect of pre-injury and injury factors such as sex, age, stage of root development, fracture type, location of fracture and severity of dislocation.

This retrospective study consisted of 400 root-fractured, splinted or non-splinted incisors in young individuals aged 7-17 years (mean = 11.5 +/- 2.7 SD) who were treated in the period 1959-1995 at the Department of Pediatric Dentistry, Eastman Dental Institute, Stockholm. Four hundred of these root fractures were diagnosed at the time of injury; and 344 teeth were splinted with either cap-splints, orthodontic appliances, bonded metal wires, proximal bonding with composite resin or bonding with a Kevlar or glass fiber splint. In 56 teeth, no splinting was carried out for various reasons. In the present study, only pre-injury and injury factors were analyzed. In a second study, treatment variables will be analyzed. The average observation period was 3.1 years +/- 2.6 SD. The clinical and radiographic findings showed that 120 teeth out of 400 teeth (30%) had healed by hard tissue fusion of the fragments. Interposition of periodontal ligament (PDL) and bone between fragments was found in 22 teeth (5%), whereas interposition of PDL alone was found in 170 teeth (43%). Finally, non-healing, with pulp necrosis and inflammatory changes between fragments, was seen in 88 teeth (22%). In a univariate and multivariate stratified analysis, a series of clinical factors were analyzed for their relation to the healing outcome with respect to pulp healing vs. pulp necrosis and type of healing (hard tissue vs. interposition of bone and/or PDL or pulp necrosis). Young age, immature root formation and positive pulp sensibility at the time of injury were found to be significantly and positively related to both pulpal healing and hard tissue repair of the fracture. The same applied to concussion or subluxation (i.e. no displacement) of the coronal fragment compared to extrusion or lateral luxation (i.e. displacement). Furthermore, no mobility vs. mobility of the coronal fragment. Healing was progressively worsened with increased millimeter diastasis between fragments. Sex was a significant factor, as girls showed more frequent hard tissue healing than boys. This relationship could possibly be explained by the fact that girls experienced trauma at an earlier age (i.e. with more immature root formation) and their traumas were of a less severe nature. Thus, the pre-injury or injury factors which had the greatest influence upon healing (i.e. whether hard tissue fusion or pulp necrosis) were: age, stage of root development (i.e. the size of the pulpal lumen at the fracture site) and mobility of the coronal fragment, dislocation of the coronal fragment and diastasis between fragments (i.e. rupture or stretching of the pulp at the fracture site).

Healing of 400 intra-alveolar root fractures. 2. Effect of treatment factors such as treatment delay, repositioning, splinting type and period and antibiotics.

This is the second part of a retrospective study of 400 root-fractured permanent incisors. In this article, the effect of various treatment procedures is analyzed. Treatment delay, i.e. treatment later than 24 h after injury, did not change the root fracture healing pattern, healing with hard tissue between fragments (HH1), interposition of bone and/or periodontal ligament (PDL) or pulp necrosis (NEC). When initial displacement did not exceed 1 mm, optimal repositioning appeared to significantly enhance both the likelihood of pulpal healing and hard tissue repair (HH1). Significant differences in healing were found among the different splinting techniques. The lowest frequency of healing was found with cap splints and the highest with fiberglass or Kevlar splints. The latter splinting procedure showed almost the same healing result as non-splinting. Comparison between non-splinting and splinting for non-displaced teeth was found to reveal no benefit from splinting. With respect to root fractures with displacement, too few cases were available for analysis. No beneficial effect of splinting periods greater than 4 weeks could be demonstrated. The administration of antibiotics had the paradoxical effect of promoting both HH1 and NEC. No explanation could be found. It was concluded that, optimal repositioning seems to favor healing. Furthermore, the chosen splinting method appears to be related to healing of root fractures, with a preference to pulp healing and healing fusion of fragments to a certain flexibility of the splint and possibly also non-traumatogenic splint application. Splinting for more than 4 weeks was not found to influence the healing pattern. A certain treatment delay (a few days) appears not to result in inferior healing. The role of antibiotics upon fracture healing is questionable.

Cardiac troponin levels following monitored epileptic seizures.

Cardiac arrhythmia associated with myocardial injury is a proposed mechanism for sudden unexplained death in epilepsy. The authors measured serial cardiac troponin levels in 11 patients after monitored seizures. Using highly sensitive assays and criteria, no troponin elevations were seen, indicating that myocardial injury does not occur during uncomplicated seizures. An elevation in postictal troponin elevations should suggest the presence of cardiac injury secondary to neurocardiogenic mechanisms or primary cardiac factors, prompting further evaluation.

Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women.

BACKGROUND: Thiazide diuretics (TDs) reduce whereas loop diuretics (LDs) increase urinary calcium. We studied the effects of different doses of a TD and LD on electrolytes, calcitropic hormones and biochemical bone markers. SUBJECTS AND METHODS: In a five-period crossover study, comparing four active doses with placebo, 40 postmenopausal women with osteopenia were treated with different doses of LD bumetanide (n = 20, 0.5-2.0 mg per day) or TD bendroflumethiazide (n = 20, 2.5-10 mg per day). Each treatment period lasted 1 week. RESULTS: Urinary calcium decreased dose-dependently in response to the bendroflumethiazide. The best hypocalciuric effect was achieved by 5 mg day-1 of bendroflumethiazide. Total plasma calcium levels increased, whereas ionised calcium at ambient pH-values decreased because of increased pH-values in response to the bendroflumethiazide. Plasma PTH levels did not change, whereas a slight dose-dependent increase occurred in plasma 1,25(OH)2D levels. As a marker of bone formation, plasma osteocalcin levels increased. Conversely, bumetanide dose-dependently increased renal calcium losses with a concomitant increase in plasma PTH and 1,25(OH)2D levels. Plasma osteocalcin levels increased and bone-specific alkaline phosphatase levels decreased dose-dependently. CONCLUSION: Whether a LD or TD is chosen as diuretic therapy affects calcium homeostasis. The effects of LDs are potentially harmful to bone. Further studies are needed to evaluate whether long-term treatment with LDs causes osteoporosis. Until then, we suggest using, if possible, a TD rather than a LD as diuretic therapy in order not to risk deleterious effects on bone metabolism.

Effects of temperature, storage time and media on periodontal and pulpal healing after replantation of incisors in monkeys.

The effect of temperature of various storage media and at varying storage periods upon periodontal ligament (PDL) and pulpal healing after tooth replantation was examined in green vervet monkeys (Cercopithecus aethiops). Mandibular lateral incisors with mature root formation were extracted and kept in dry storage at 22, 4 and -18 degrees C; in saline at 37, 22, 4 and -18 degrees C; or in saliva (i.e. in the buccal vestibule) at 37 degrees C for either 60 or 120 min prior to replantation. The animals were sacrificed 8 weeks after replantation and the replanted teeth examined histometrically. The following histological parameters were registered for each tooth: normal PDL, surface resorption, inflammatory resorption, replacement resorption (ankylosis), downgrowth of pocket epithelium, periapical inflammatory changes, and the extent of vital pulp. A total of 125 replanted teeth were examined. Storage in saliva at 37 degrees C showed a similar amount of normal PDL compared to saline storage for both 60 and 120 min. Saline storage for 60 or 120 min showed no difference in the extent of normal PDL when storage was compared at 37, 22 and 4 degrees C. However, storage at -18 degrees C resulted in significantly less normal PDL than storage at other temperatures. Dry storage for 60 min showed significantly less root resorption at 4 degrees C compared to 22 degrees C. Furthermore, dry storage at -18 degrees C showed significantly less normal PDL than storage at 4 degrees C. When the dry storage period was extended to 120 min, no difference was found between 22, 4 and -18 degrees C. It is concluded that the temperature (above 0 degrees C) of the storage medium is of importance only for dry storage and in such a situation only for shorter extra-alveolar periods, i.e. for 60-min storage and not for 120 min, where extensive destruction of the PDL always takes place. It is suggested that the temperature effect of 4 degrees C could be related to less evaporation from the PDL and thereby less damage to the PDL cells or a strict temperature effect upon cell metabolism. Pulp healing in all the cases was limited to the entrance of the pulp canal, and no significant pattern was found between storage media, time and temperature.

Statins decrease bone turnover in postmenopausal women: a cross-sectional study.

BACKGROUND: Statins have been suggested as potential agents in the management of osteoporosis. Reviews of medical records have shown an increased bone mass and some studies have shown a reduced occurrence of fractures in subjects on long-term treatment with statins. We studied the effects of treatment with statins on calcium homeostasis, bone turnover and bone mineral density. DESIGN: In a cross-sectional design, plasma levels of parathyroid hormone (PTH) and biochemical markers of bone turnover, bone mineral density (BMD) and body composition (fat- and lean tissue-mass) were measured in 140 postmenopausal women who had been treated with a statin for more than 2 years (median 4 years) and compared to 140 age- and gender-matched, population-based controls. RESULTS: Plasma levels of bone turnover markers were lower in the statin-treated subjects than in the controls: osteocalcin (-9%, P = 0.03), bone-specific alkaline phosphatase (-14%, P < 0.01), and C-terminal telopeptide of type I collagen (-11%, P < 0.01). On the other hand, plasma PTH levels were 16% higher in the statin-treated subjects than in the controls (P < 0.01). However, body composition and BMD at the lumbar spine, hip, forearm and whole body did not differ between the two groups. No correlation could be demonstrated between changes in biochemical quantities and dose or duration of statin use. CONCLUSION: Our data show that statins affect the function of bone cells. Most likely, the effect is antiresorptive.

Effect of treatment delay upon pulp and periodontal healing of traumatic dental injuries -- a review article.

Based on an analysis of the literature concerning parameters influencing the prognosis of traumatic dental injuries, few studies were found to have examined possible relationships between treatment delay and pulpal and periodontal ligament healing complications. It has been commonly accepted that all injuries should be treated on an emergency basis, for the comfort of the patient and also to reduce wound healing complications. For practical and especially economic reasons, various approaches can be selected to fulfill such a demand, such as acute treatment (i.e. within a few hours), subacute (i.e. within the first 24 h), and delayed (i.e. after the first 24 h). In this survey the consequences of treatment delay on pulpal and periodontal healing have been analyzed for the various dental trauma groups. Applying such a treatment approach to the various types of injuries, the following treatment guidelines can be recommended, based on our present rather limited knowledge of the effect of treatment delay upon wound healing. Crown and crown/root fractures: Subacute or delayed approach. Root fractures: Acute or subacute approach. Alveolar fractures: Acute approach (evidence however questionable). Concussion and subluxation: Subacute approach. Extrusion and lateral luxation: Acute or subacute approach (evidence however questionable). Intrusion: Subacute approach (evidence however questionable). Avulsion: If the tooth is not replanted at the time of injury, acute approach; otherwise subacute. Primary tooth injury: Subacute approach, unless the primary tooth is displaced into the follicle of the permanent tooth or occlusal problems are present; in the latter instances, an acute approach should be chosen. These treatment guidelines are based on very limited evidence from the literature and should be revised as soon as more evidence about the effect of treatment delay becomes available.

Loop diuretics alter the diurnal rhythm of endogenous parathyroid hormone secretion. A randomized-controlled study on the effects of loop- and thiazide-diuretics on the diurnal rhythms of calcitropic hormones and biochemical bone markers in postmenopausal women.

BACKGROUND: Thiazide diuretics (TD) reduce urinary calcium, bone loss and fracture risk. Loop diuretics (LD) may have opposite effects. These effects could depend on induced rhythmic changes in bone and calcium homeostasis. DESIGN: After a run-in period of 7 days, we studied (in a factorial design) the diurnal rhythms of plasma levels of calcium, phosphate, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D and osteocalcin, as well as renal excretions rates of calcium, phosphate, and cross-linked N-terminal telopeptide of type 1 collagen (NTx) in 50 postmenopausal women randomized to treatment with either a thiazide diuretic (TD; bendroflumethiazide, n = 14), a loop diuretic (LD; bumetanide, n = 13), LD plus TD (bendroflumethiazide plus bumetanide, n = 11), or placebo (n = 12). RESULTS: In all four groups, all measured quantities showed a diurnal variation. LD caused a steep increase, with a subsequent decrease, in urinary calcium and plasma PTH. The mean 24 h plasma PTH concentration was increased (8.5 +/- 0.9 mmol L-1) compared with placebo (4.4 +/- 0.4 mmol L-1), whereas net 24 h renal calcium excretion did not differ from that of the placebo group due to a rebound hypocalciuria. Compared with placebo, diurnal rhythms of plasma phosphate and osteocalcin were changed with an increase during daytime and a decrease during the night. TD did not alter the diurnal rhythm of any of the measured quantities. However, the 24-h renal calcium excretion decreased, whereas the mean 24-h plasma calcium concentration increased without PTH suppression. LD plus TD caused changes similar to those observed with LD alone. CONCLUSION: One daily dose of LD increases parathyroid activity with alterations in the diurnal pattern of osteocalcin. This could indicate a potential anabolic effect of LD.

Effects of thiazide- and loop-diuretics, alone or in combination, on calcitropic hormones and biochemical bone markers: a randomized controlled study.

OBJECTIVE: Diuretics are commonly used drugs that in addition to their effect on the cardiovascular system also affect calcium homeostasis and bone metabolism. We evaluated the effects of loop diuretics (LD) and thiazide diuretics (TD) on calcitropic hormones and biochemical bone markers. DESIGN: A total of 50 postmenopausal women were randomized to 7 days of treatment with either the TD bendroflumethiazide, the LD bumetanide, bendroflumethiazide plus bumetanide, or placebo. Blood and urine (24 h) were sampled on each day. Statistical inferences were made versus the concomitant changes in the placebo group. RESULTS: Bendroflumethiazide increased the tubular reabsorption of calcium (TRCa) (+0.46 +/- 0.11%, P=0.009), plasma levels of parathyroid hormones (PTH) (+24 +/- 10%, P=0.06), and 1,25(OH)2D (+12 +/- 6%, P=0.03). Bumetanide decreased the TRCa (-0.5 +/- 0.1%, P=0.01) and increased plasma PTH and 1,25(OH)2D levels (+27 +/- 9%, P=0.02 and +36 +/- 12%, P=0.006, respectively). Treatment with either of the drugs did not alter plasma calcium, osteocalcin, bone alkaline phosphatase (bone-ALP) or urinary NTx/creatinine ratio. However, treatment with both drugs caused an increased plasma calcium level (+2.7 +/- 1.0%, P=0.007) and decreased plasma levels of bone-ALP (-21 +/- 3%, P=0.001), osteocalcin (-6 +/- 3%, P=0.03), and urinary NTx/creatinine ratio (-39 +/- 6%, P=0.001). CONCLUSION: Calcium homeostasis and bone metabolism are to a major degree influenced by diuretic treatment. Surprisingly, LD and TD exerted a similar effect on calcitropic hormones despite their opposite effects on the renal calcium excretion. In clinical practice, treatment with diuretics has to be considered as a cause of parathyroid stimulation.

Drug therapy in the elderly: what doctors believe and patients actually do.

AIMS: To examine the medication adherence among old persons living in their own homes, to assess their knowledge of their medication, and to indicate target areas for intervention. METHODS: A cross-sectional study of data collected from randomly selected samples of 348 persons, aged 75 years recruited from a population-based register in the municipality of Aarhus, Denmark. Information on all drugs was collected from the subjects during a home visit, and their drug storage was examined. Information was collected from the general practitioners (GP). The measures of adherence were scores of agreements between the GPs' lists and the subjects' actual drug consumption. RESULTS: We found disagreement between the drug information collected from the study population and from the GPs: concerning drugs in 22% of the study-population, concerning doses in 71%, and concerning regimens prescribed by the GP in 66%. Twenty-four percent stated that they did not always follow prescriptions. Most of the deviations from prescriptions were toward lower doses and less frequent drug intake. The drugs most often involved in deviations were hypnotics, analgesics, bronchodilators and diuretics. Sixty percent of the participants knew the purpose of medication, and 21% knew the consequences of omission of the drugs. Less than 6% of the subjects knew about the toxic risks, side-effects, or potential drug interactions. The participants' knowledge of the drugs was positively associated with their adherence. We found a correlation between an increased number of prescribed frequency of drug intake per day and deviation from the regimen (r = 0.25, P = 0.01). There was a positive association between nonadherence and the use of three or more drugs (odds ratio (OR) 2.5; 95% confidence interval (CI) 1.5,4.1), prescriptions from more than one doctor (OR 2.5; 95% CI 1.3,4.8), and probability of dementia (OR 9.0; 95% CI 1.1,72.5). Moreover compliance aids facilitated adherence (OR 4.4; 95% CI 1.6,12.3). Persons living alone were more prone to medication errors (OR 2.0; 95% CI 1.1,3.5). CONCLUSIONS: A differentiated evaluation of adherence by considering the drug, the dose, and the regimen separately produced quantifiable data concerning the subjects' medication habits. Non-adherence ranged from 20 to 70% depending on the measuring method. The participants' knowledge of the treatment was poor. Our results suggest that better information on medication and the use of compliance aids may prevent nonadherence. Special attention should be paid to persons receiving three or more drugs, living alone, receiving drugs from other doctors, and to persons with predementia symptoms, as they are at higher risk of nonadherence.

Pulpal healing following acute dental trauma: clinical and radiographic review.

Successful treatment of tooth luxations, crown fractures, and root fractures is often compromised by the emergency nature of the injury. Precise radiographic and clinical evaluation is required to facilitate healing and treatment selection. While traditional treatment protocols indicate that dental injuries implying pulpal ischemia require immediate endodontic therapy to avoid healing complications, the clinical investigations discussed herein suggest that a variety of etiologies for pulp survival/pulp necrosis exist. This article discusses the long-term prognosis of pulp necrosis following traumatic dental injuries, and clinical and radiographic criteria for its diagnosis.

The consumption of drugs by 75-year-old individuals living in their own homes.

OBJECTIVE: To examine the drug consumption and the extent of polypharmacy (defined as daily intake of three or more drugs) among 75-year-old persons living in their own homes and to point out potential problems associated with it. METHODS: Information on the intake of all drugs was collected from 492 subjects randomly selected. The subjects were interviewed at home, and their drug storage was examined. Information was also collected from the general practitioners (GPs) and from prescription databases. Database information comprised prescribed drugs used by the study population and the background population. RESULTS: Eighty-seven percent of the study population received prescribed drugs and 72% used over-the-counter (OTC) drugs. Only 3% of the subjects did not take any drugs. Eighty percent of females and 60% of males used central nervous system (CNS) drugs, the most commonly used category. The subjects took on average 4.2 different prescribed drugs and 2.5 OTC drugs. Sixty percent used three or more prescribed drugs and 34% used five or more. Thirty percent used three or more OTC drugs. Seventeen percent had prescribed drugs not in use at the time of the examination in their drug storage. Twenty-five percent of the prescribed drugs were used without the GPs' knowledge. Thirty-one percent of the study population received prescribed drugs from two or more physicians. Potential drug interactions with clinical significance were found among 15.3% of the participants and were positively correlated to polypharmacy. CONCLUSION: Almost all 75-year-old persons receive drugs. The observed polypharmacy may increase drug-related risks. The discrepancies between the GPs' knowledge of their patients' medication and the actual intake may involve a potential risk. A better registration of the patients' total medication and the implementation of a common medication database for the use of all involved physicians may improve medication and reduce risks.

Increased natriuretic efficiency of furosemide in rats with carbon tetrachloride-induced cirrhosis.

The authors examined the natriuretic efficiency of furosemide in rats with cirrhosis induced by carbon tetrachloride (CCl(4)). Rats were treated for 17 weeks with intraperitoneal injections of CCl(4) in groundnut oil twice a week throughout the study. Control rats were treated with vehicle (groundnut oil). Studies in metabolic cages showed that sodium retention was present from week 14. Renal clearance experiments were performed in chronically, instrumented conscious rats at the end of week 14 and at the termination of the study (end week 16) when ascites and hyponatremia were present. After 14 weeks, cirrhotic rats had sodium retention along with increased renal plasma flow, normal GFR, normal renal lithium handling, and a significantly increased diuretic (+41% vs. control) and natriuretic (+56% vs. control) response to a test dose furosemide (7.5 mg/kg b.w., intravenously). The natriuretic efficiency of furosemide, i.e., the natriuresis expressed relative to the furosemide excretion rate (triangle upU(Na)V/U(FUR)V) was increased by 51% versus control. After 17 weeks, ascites and hyponatremia had developed, and significant decreases in renal plasma flow (-33%), GFR (-30%), and fractional lithium excretion (-44%) were observed. At this stage urinary recovery of furosemide was significantly decreased and the diuretic (-27% vs. Control) and natriuretic (-38% vs. control) responses to furosemide were significantly impaired. However, the increased natriuretic efficiency of furosemide was still present (+34% vs. control). Together these results suggest that increased sodium reabsorption in the thick ascending limb of Henle's loop is involved in the renal sodium retention in cirrhosis in rats that eventually results in decompensation with the formation of ascites.

Postoperative hepatic catabolic stress response in patients with cirrhosis and chronic hepatitis.

Open (OC) or laparoscopic (LC) cholecystectomy is considered a relative contraindication in patients with liver cirrhosis. The effect of LC and OC on the hepatic catabolic stress response was studied in patients with postnecrotic liver cirrhosis and chronic hepatitis to define the most suitable procedure from a metabolic point of view. Altogether 14 patients with cirrhosis and 14 with chronic hepatitis were randomized to LC or OC (n = 7 in each group). The increase in the functional hepatic nitrogen clearance (FHNC) was quantified. Changes in glucose, insulin, glucagon, cortisol, epinephrine, norepinephrine, and prostaglandin E(2) (PGE(2)) were observed. There was no difference in FHNC between LC and OC in any of the patients. Among cirrhotic patients OC caused a 132% increase in FHNC (p < 0.05) and among the hepatitis patients a 69% increase (p < 0.05). In contrast, there was no significant increase following LC in any of the patients. OC increased fasting glucose and insulin in the hepatitis patients (p < 0.01 and p < 0.001, respectively) and in the cirrhosis group (p < 0.01 and p < 0.05, respectively). Alanine stimulation increased glucose in hepatitis patients after OC (p < 0.05) and after LC (p < 0.01). Stimulated glucagon increased after OC in the hepatitis group (p < 0.05). During stimulation cortisol was higher following LC in hepatitis patients (p < 0.01) and cirrhotic patients (p < 0.05). Fasting PGE(2) was down-regulated after LC in hepatitis patients (p < 0.05) and cirrhotic patients (p < 0.01) and after OC in the hepatitis group (p < 0.001). FHNC is similar after LC and OC. Thus from a metabolic point of view, LC has no advantage over OC.

Long-term prognosis of crown-fractured permanent incisors. The effect of stage of root development and associated luxation injury.

OBJECTIVES: The aim of the present study was to investigate pulp healing responses following crown fracture with and without pulp exposure as well as with and without associated luxation injury and in relation to stage of root development. PATIENT MATERIAL AND METHODS: The long-term prognosis was examined for 455 permanent teeth with crown fractures, 352 (246 with associated luxation injury) without pulpal involvement and 103 (69 with associated luxation injury) with pulp exposures. Initial treatment for all patients was provided by on-call oral surgeons at the emergency service, University Hospital (Rigshospitalet), Copenhagen. In fractures without pulpal involvement, dentin was covered by a hard-setting calcium hydroxide cement (Dycal), marginal enamel acid-etched (phosphoric acid gel), then covered with a temporary crown and bridge material. In the case of pulp exposure, pulp capping or partial pulpotomy was performed. Thereafter treatment was identical to the first group. Patients were then referred to their own dentist for resin composite restoration. RESULTS: Patients were monitored for normal pulp healing or healing complications for up to 17 years after injury (x = 2.3 years, range 0.2-17.0 years, SD + 2.7). Pulp healing was registered and classified into pulp survival with no radiographic change (PS), pulp canal obliteration (PCO) and pulp necrosis (PN). Healing was related to the following clinical factors: stage of root development at the time of injury, associated damage to the periodontium at time of injury (luxation) and time interval from injury until initial treatment. Crown fractures with or without pulp exposure and no concomitant luxation injury showed PS in 99%, PCO in 1% and PN in 0%. Crown fractures with concomitant luxation showed PS in 70%, PCO in 5% and PN in 25%. An associated damage to the periodontal ligament significantly increased the likelihood of pulp necrosis from 0% to 28% (P < 0.001) in teeth with only enamel and dentin exposure and from 0% to 14% (P < 0.001) in teeth with pulp exposure. CONCLUSIONS: In the case of concomitant luxation injuries, the stage of root development played an important role in the risk of pulp necrosis after crown fracture. However, the primary factor related to pulp healing events after crown fracture appears to be compromised pulp circulation due to concomitant luxation injuries.