1997 Volvo Award winner in clinical studies. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective, randomized study comparing decompressive laminectomy and arthrodesis with and without spinal instrumentation

STUDY DESIGN: This prospective study analyzed the influence of transpedicular instrumented on the operative treatment of patients with degenerative spondylolisthesis and spinal stenosis. OBJECTIVES: To determine whether the addition of transpedicular instrumented improves the clinical outcome and fusion rate of patients undergoing posterolateral fusion after decompression for spinal stenosis with concomitant degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: Decompression is often necessary in the treatment of symptomatic patients who have degenerative spondylolisthesis and spinal stenosis. Results of recent studies demonstrated that outcomes are significantly improved if posterolateral arthrodesis is performed at the listhesed level. A meta-analysis of the literature concluded that adjunctive spinal instrumentation for this procedure can enhance the fusion rate, although the effect on clinical outcome remains uncertain. METHODS: Seventy-six patients who had symptomatic spinal stenosis associated with degenerative lumbar spondylolisthesis were prospectively studied. All patients underwent posterior decompression with concomitant posterolateral intertransverse process arthrodesis. The patients were randomized to a segmental transpedicular instrumented or noninstrumented group. RESULTS: Sixty-seven patients were available for a 2-year follow-up. Clinical outcome was excellent or good in 76% of the patients in whom instrumentation was placed and in 85% of those in whom no instrumentation was placed (P = 0.45). Successful arthrodesis occurred in 82% of the instrumented cases versus 45% of the noninstrumented cases (P = 0.0015). Overall, successful fusion did not influence patient outcome (P = 0.435). CONCLUSIONS: In patients undergoing single-level posterolateral fusion for degenerative spondylolisthesis with spinal stenosis, the use of pedicle screws may lead to a higher fusion rate, but clinical outcome shows no improvement in pain in the back and lower limbs.     

Lumbar disk prolapse surgery with or without free fat transplantation. A prospective triple-blind randomized study

The aim of this prospective triple-blind randomized study was to determine if a free fat transplant used in operation in lumbar disc herniation could reduce the degree of intraspinal scar tissue and to evaluate whether the scar tissue could lead to symptoms. Ninety-nine patients were subsequently examined after median 376 days. The clinical outcome was scored using the Low Back Pain Rating Scale. Enhanced CT-scanning was assessed regarding the degree of scar tissue and survival of the fat transplant. There was no difference in the clinical outcome between the two groups. Significantly fewer had dural scarring in the group who had a free fat transplantation, but there was no difference regarding the degree of radicular scarring. The transplant was shown on CT-scan at the follow-up examination in 66% of the patients who had a fat transplantation. Free fat transplantation can reduce the degree of dural scar tissue after operation for lumbal disc herniation, but does not result in a clinically better outcome.     

Operative treatment of fractures of the tibial plafond. A randomized, prospective study

We performed a randomized, prospective study to compare the results of two methods for the operative fixation of fractures of the tibial plafond. Surgeons were assigned to a group on the basis of the operation that they preferred (randomized-surgeon design). In the first group, which consisted of eighteen patients, open reduction and internal fixation of both the tibia and the fibula was performed through two separate incisions. An additional patient, who had an intact fibula, had fixation of the tibia only through an anteromedial incision. The second group consisted of twenty patients who were managed with external fixation with or without limited internal fixation (a fibular plate or tibial interfragmentary screws). Ten (26 per cent) of the thirty-nine fractures were open, and seventeen (44 per cent) were type III according to the classification of Rüedi and Allg?wer. There were fifteen operative complications in seven patients who had been managed with open reduction and internal fixation and four complications in four patients who had been managed with external fixation. All but four of the complications were infection or dehiscence of the wound that had developed within four months after the initial operation. The complications after open reduction and internal fixation tended to be more severe, and amputation was eventually done in three patients in this group. At a minimum of two years postoperatively (average, thirty-nine months; range, twenty-five to fifty-one months), the average clinical score was lower for the patients who had had a type-II or III fracture, regardless of the type of treatment. With the numbers available, no significant difference was found between the average clinical scores for the two groups. All of the patients, in both groups, who had had a type-II or III fracture had some degree of osteoarthrosis on plain radiographs at the time of the latest follow-up. With the numbers available, there was no significant difference between the two groups with regard to the osteoarthrotic changes. We concluded that external fixation is a satisfactory method of treatment for fractures of the tibial plafond and is associated with fewer complications than internal fixation.     

Cost-effective appendectomy. Open or laparoscopic? A prospective randomized study

BACKGROUND: Laparoscopic hernia repair has often been criticized for its high costs. METHODS: To compare the costs of laparoscopic and open hernia repair, 40 patients were randomized for either transabdominal laparoscopic or Lichtenstein mesh repair (under local anesthesia) in a day-case surgery unit. RESULTS: Median operative times for the laparoscopic and open groups were 62 and 65 min, respectively. Postoperative pain was comparable for the two groups. The period before return to normal life was 14 days in the laparoscopic group and 21 days in the open group. The hospital costs were 2051 FIM ($1 US = 4.6 FIM) higher in the laparoscopic group, but the total costs for employed patients (including expenses due to lost work days) were lower. CONCLUSION: Although the Lichtenstein operation is cheaper for the hospital, the total costs for working patients are lower with the laparoscopic technique, when the cost of lost work days is factored into overall expense.     

Cyclosporine A in the treatment of early rheumatoid arthritis. A prospective, randomized 24-month study

OBJECTIVE: To investigate the efficacy, tolerability and safety of cyclosporine A (CSA) in early rheumatoid arthritis (RA) patients. METHODS: Patients with an early diagnosis of RA, a disease duration of less than 3 years, and without prior disease modifying antirheumatic drug (DMARD) treatment were studied. They randomly received oral CSA (3 mg/kg/day) or oral methotrexate (MTX) (0.15 mg/kg/week). In addition, all patients in both groups received oral prednisone (7.5 mg/day). RESULTS: Fifty-two patients were assigned to the CSA group and 51 to the MTX group. After 24 months of treatment, 48 patients from the CSA group and 48 from the MTX group showed significant clinical improvement. This was evaluated by the duration of morning stiffness, grip strength, the total joint count, joint swelling, and joint tenderness and pain, compared to pre-treatment values. The clinical improvement was also associated with a significant decrease in ESR and CRP values in both groups. No significant radiological deterioration was observed in the CSA patients compared to those treated with MTX after 24 months. Four patients from the CSA group dropped out of the study, two because of a synovitis flare, one because of severe hypertrichosis and one because of severe gingival hyperplasia. Three patients from the MTX group withdrew, one because of disease flare-up and two because of gastrointestinal disturbances. CONCLUSION: Early immunointervention in RA patients appears to be crucial to limit the development of joint damage. Cyclosporine A appears to be effective, well tolerated and safe in the long-term treatment of RA and can therefore be used as a first immunomodulatory drug in the armamentarium for the treatment of RA.     

Hypnotic taper with or without self-help treatment of insomnia: A randomized clinical trial.

This study aimed to assess the efficacy of a minimal intervention focusing on hypnotic discontinuation and cognitive-behavioral treatment (CBT) for insomnia. Fifty-three adult chronic users of hypnotics were randomly assigned to an 8-week hypnotic taper program, used alone or combined with a self-help CBT. Weekly hypnotic use decreased in both conditions, from a nearly nightly use at baseline to less than once a week at posttreatment. Nightly dosage (in lorazepam equivalent) decreased from 1.67 mg to 0.12 mg. Participants who received CBT improved their sleep efficiency by 8%, whereas those who did not remained stable. Total wake time decreased by 52 min among CBT participants and increased by 13 min among those receiving the taper schedule alone. Total sleep time remained stable throughout withdrawal in both CBT and taper conditions. The present findings suggest that a systematic withdrawal schedule might be sufficient in helping chronic users stop their hypnotic medication. The addition of a self-help treatment focusing on insomnia, a readily available and cost-effective alternative to individual psychotherapy, produced greater sleep improvement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

HDR and MDR intracavitary treatment for carcinoma of the uterine cervix. A prospective randomized study

The multiple goals theory of conflict management (Ohbuchi & Tedeschi, in press) postulated that participants in a conflict pursue to achieve resource goals (economic and personal resources) and social goals (relationship, identity, justice, and power-hostility). The hypotheses based on this theory were examined by the episode method, in which 207 university students were asked to rate their recent experiences of interpersonal conflicts in terms of participants' attributes, goals, and tactics. More than 80% of the subjects answered that they were motivated to achieve multiple goals in their attempts to resolve the conflicts. Social goals were found to be more strongly activated, and economic resource goals were least strongly activated. Regression analyses revealed that the effects of participants' attributes on tactical preference were mediated by goals.     

Concho-antropexy or total inferior turbinectomy for hypertrophy of the inferior turbinates? A prospective randomized study

Twenty-five patients with bilateral nasal obstruction due to hypertrophy of the inferior turbinates were entered into a prospective study to compare the efficacy and the associated complications of total inferior turbinectomy and concho-antropexy. We found no significant statistical difference in the efficacy of these procedures in relieving nasal obstruction and discharge (p > 0.5). Total inferior turbinectomy was associated with more post-operative pain (p < 0.05) and with long-term dryness and crusting (p < 0.05) which were statistically significant. This is the first trial where concho-antropexy and total inferior turbinectomy are compared.     

Inactivation of food microorganisms by high-pressure carbon dioxide treatment with or without explosive decompression

In order to elucidate the sterilization mechanism underlying the explosive decompression system, baker's yeast was pressurized with CO2, N2O, N2, or Ar gas at 40 atm and 40 degrees C for 4h, and then explosively discharged. The survival ratio was markedly decreased only by the treatments with CO2 and N2O, which are relatively soluble gases in water, suggesting that the microorganisms' death may be highly correlated with gas absorption by the cells. Lower decompression rates to atmospheric pressure, however, led to neither any lower reduction of remaining cells nor any smaller release of total cellular proteins. Furthermore, operating with a longer treatment time and smaller number of repetitions was usually more lethal than with a shorter time and more frequent repetition. From these results, most of the yeast cells appear to have been sterilized during the pressurization process. The spore cells of B. megaterium are considered to have been killed in a somewhat different manner, because of their distinct sensitivity to the applied gases.     

A clinical comparison of two triphasic oral contraceptives with levonorgestrel or norethindrone: a prospective, randomized, single-blind study

Menstrual bleeding patterns were investigated in young women taking either a levonorgestrel triphasic, Triquilar, or a norethindrone triphasic, Ortho 7/7/7, two commonly prescribed low-dose oral contraceptives. The levonorgestrel triphasic contains ethinyl estradiol (EE) 30 micrograms + levonorgestrel (LNG) 50 micrograms for the first six days, EE 40 micrograms + LNG 75 micrograms for the following five days, and EE 30 micrograms + LNG 125 micrograms for the last ten days. The norethindrone triphasic contains EE 35 micrograms + norethindrone (NET) 0.5 mg for the first seven days, EE 35 micrograms + NET 0.75 mg for the following seven days and EE 35 micrograms + NET 1.0 mg for the last seven days. Three hundred women from 16 to 25 years of age were randomized to the levonorgestrel triphasic (n = 150) or the norethindrone triphasic (n = 150) groups. Assessments were made from daily diary cards and from bimonthly investigator interviews over 6 pill cycles. The results showed a higher incidence of intermenstrual bleeding (breakthrough bleeding and/or spotting) in the norethindrone triphasic group (NET group) than in the levonorgestrel triphasic group (LNG group): 44.9% of patients (66/147) randomized to the LNG group reported intermenstrual bleeding one or more times during the study compared with 61.9% (91/147) randomized to the NET group (p = 0.0036). Furthermore, in subjects who did not miss any pills, the proportion of patients with intermenstrual bleeding in each cycle was significantly greater (p < 0.02, cycles 1-4, 6; p > 0.05, cycle 5) and was experienced for more days per cycle (p < 0.05, cycle 1) and for more cycles per patient (p < 0.05, 5 cycles) in the NET group compared with the LNG group. Intermenstrual bleeding was also less frequently observed in the LNG group than in the NET group in patients who missed pills (p < 0.05, cycles 3, 5 and 6). In addition, early withdrawal bleeding occurred more often in the NET group than in the LNG group (p < 0.05, cycles 1, 3 and 4). The incidence of amenorrhea was similar in both groups. These results demonstrate a significantly lower incidence of intermenstrual bleeding and therefore better cycle control with the levonorgestrel triphasic Triquilar, compared with the norethindrone triphasic Ortho 7/7/7.     

Anterior cervical decompression and arthrodesis for the treatment of cervical spondylotic myelopathy. Two to seventeen-year follow-up

We reviewed the cases of 108 patients with cervical spondylotic myelopathy who had been managed with anterior decompression and arthrodesis at our institution. Operative treatment consisted of anterior discectomy, partial corpectomy, or subtotal corpectomy at one level or more, followed by placement of autogenous bone graft from the iliac crest or the fibula. At the latest follow-up examination, thirty-eight of the eighty-two patients who had had a preoperative gait abnormality had a normal gait, thirty-three had an improvement in gait, six had no change, four had improvement and later deterioration, and one had a worse gait abnormality. Of the eighty-seven patients who had had a preoperative motor deficit, fifty-four had complete recovery; twenty-six, partial recovery; six, no change; and one had a worse deficit. The average grade according to the system of Nurick improved from 2.4 preoperatively to 1.2 (range, 0.0 to 5.0) postoperatively. A pseudarthrosis developed in sixteen patients, thirteen of whom had had a multilevel discectomy. Only one of thirty-eight arthrodeses that had been performed with use of a fibular strut graft was followed by a non-union. An unsatisfactory outcome with respect to pain was significantly associated with pseudarthrosis (p < 0.001). The development of complications other than non-union was associated with a history of one previous operative procedure or more (p = 0.005). Recurrent myelopathy was rare, but when it occurred it was associated with a pseudarthrosis or stenosis at a new level. The strongest predictive factor for recovery from myelopathy was the severity of the myelopathy before the operative intervention--that is, better preoperative neurological function was associated with a better neurological outcome. Anterior decompression and arthrodesis with autogenous bone-grafting can be performed safely, and is associated with a high rate of neurological recovery, functional improvement, and pain relief, in patients who have cervical spondylotic myelopathy.     

Opioid therapy for chronic noncancer back pain. A randomized prospective study

STUDY DESIGN: A randomized, open, long-term, repeated-dose comparison of an anti-inflammatory drug and two opioid regimens in 36 patients with back pain. OBJECTIVES: To examine the long-term safety and efficacy of chronic opioid therapy in a randomized trial of patients with back pain. METHODS: All participants underwent a 4-week washout period of no opioid medication before being randomly assigned to one of three treatment regimens for 16 weeks: 1) naproxen only, 2) set-dose oxycodone, or 3) titrated-dose oxycodone and sustained-release morphine sulfate. All patients then were assigned to a titrated dose of opioids for 16 weeks and then gradually tapered off their medication for 12 weeks. Finally, all participants were monitored for a 1-month posttreatment washout period. Each patient was called once a week for a report on pain, activity, mood, medication, hours awake, and adverse effects and was monitored carefully for signs of abuse and noncompliance. RESULTS: Weekly reports during the experimental phase showed the titrated-dose group to have less pain (P < 0.001) and less emotional distress (P < 0.001) than the other two groups. Both opioid groups were significantly different from the naproxen-only group. During the titration phase, patients also reported significantly less pain and improved mood. Few differences were found in activity or hours asleep, or between average pretreatment and posttreatment phone-interview and questionnaire variables. No adverse events occurred, and only one participant showed signs of abuse behavior. CONCLUSIONS: The results suggest that opioid therapy has a positive effect on pain and mood but little effect on activity and sleep. Opioid therapy for chronic back pain was used without significant risk of abuse. However, tapered-off opioid treatment is palliative and without long-term benefit.     

Participant modeling with or without cognitive treatment for phobias.

To determine whether cognitive treatment would enhance the effectiveness of participant modeling (PM) treatment for phobias, 36 subjects phobic to dogs and cats were given either PM alone, PM with self-instructional training, PM with self-verbalizations ("thinking aloud"), or placebo treatment. The three PM treatments produced substantial and equivalent improvement in behavior at posttest, in contrast to the placebo group, which did not change. At follow-up, the combined PM/self instructional training group showed more phobic behavior and lower self-efficacy than the other PM groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study

Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a standard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), between-group comparison showed no significant differences at any of the follow-up evaluations. The proportion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening.     

Sitting or supine stereotaxic core biopsy of the breast? A comparison based on a randomized, prospective study

OBJECTIVE/MATERIAL AND METHODS: In a prospective randomized study, the techniques of stereotactic breast biopsies in prone and sitting position were compared. Part of the data has already been published. A total of 103 women underwent stereotactic breast biopsies, either prone (n = 51; using TRC-Mammotest, Sweden) or in the sitting position (n = 52; using Stereotix 2, General Electric Medical Systems, Milwaukee, Wisconsin, USA). With the help of pre- and post-biopsy questionnaires, anxiety, pain, and subjective experience were recorded in all patients. Vasovagal reactions were scored from 0 to 2 according to their severity. All biopsy results were verified by surgery. The specificities and sensitivities for the two positions were calculated and statistically compared. RESULTS: With regard to overall tolerance no statistically significant difference between biopsies performed in the sitting or the prone position was noted. Significantly more patients (p = 0.04) in the prone position stated they would prefer premedication prior to a repeat biopsy. Three patients (prone; n = 1; sitting; n = 2) fainted during the procedure. There was no statistically significant difference between the two biopsy positions regarding sensitivity (95%) and specificity (100%). CONCLUSIONS: More attention should be paid to patient care and, especially, preintervention information. Biopsies in the prone or sitting position are equally well tolerated. Somatic reactions are not a major problem during breast biopsy. Success and validity are independent of the biopsy position.     

Early active training after lumbar discectomy. A prospective, randomized, and controlled study

STUDY DESIGN: A prospective, randomized, and controlled study was conducted. OBJECTIVES: To evaluate two training programs, both of which started immediately after lumbar discectomy. SUMMARY OF BACKGROUND DATA: In previous studies, patients began physiotherapy between 4 weeks and 60 months after surgery. No studies have been conducted to evaluate a physiotherapy program that begins immediately after surgery. METHOD: Twenty-six patients were treated according to an early active training program. Twenty-six patients were treated with a traditional, less active training program (control group). All patients were examined immediately before and after surgery and 3, 6, 12, and 52 weeks after surgery by an unbiased observer. Two years after surgery, patients completed a questionnaire. Range of motion of the lumbar spine and straight leg raising were measured. pain intensity and location was measured by a visual analog scale. The duration of sick leave was documented. RESULTS: Six and 12 weeks after surgery, patients with dominating residual leg pain had significantly less intense pain in the early active training group than those in the control group (P < 0.05). Twelve weeks after surgery, range of motion of the lumbar spine was significantly more increased in the early active training group (P < 0.01). One year after surgery, there was no significant difference between the groups regarding the duration of sick leave, results in a positive straight leg raising, or pain intensity. Twenty-two (88%) patients in the early active training group and 16 (67%) in the control group were satisfied with the treatment outcome 2 years after surgery (P < 0.10). CONCLUSIONS: Patients rehabilitated according to the early active training program had a better short-term outcome of objective values. At 2 years' follow-up, more patients were satisfied with the result of the operation. The early active treatment program is recommended.     

Octreotide: effective treatment for hyperparathyroidism? A prospective, randomized, controlled clinical trial

Although clinical and electrophysiological evidence indicates that the amygdaloid body plays an important role in the pathogenesis of temporal lobe epilepsy, there are very few detailed data on histopathological changes in this nucleus in epilepsy patients. In the present study we have examined the lateral nucleus of the amygdaloid body in 70 surgical specimens from patients with temporal lobe epilepsy and in 10 control specimens with respect to neuronal density and gliosis. The results were compared to the neuronal loss in the hippocampal formation. Our goal was to examine the pathological alterations of the amygdaloid body and their correlation with other morphological changes in temporal lobe epilepsy. In epilepsy patients with Ammon's horn sclerosis or focal lesions of the temporal lobe, the neuronal density of the lateral amygdaloid nucleus was significantly decreased as compared to normal controls (P < 0.001). Overall, the mean volumetric density in epilepsy patients was reduced to 59% of that in normal individuals. There was no correlation between the neuronal density in the lateral amygdaloid nucleus and that in the different segments of the hippocampal formation or to the age at onset or the duration of epilepsy. The neuronal loss of the amygdaloid nucleus correlated well with the presence of fibrillary gliosis. Our findings demonstrate that the amygdaloid body is severely altered in most patients with temporal lobe epilepsy and that these changes are independent of those in the hippocampus. The presence of neuronal loss and gliosis in the amygdaloid nucleus of patients with focal lesions but no Ammon's horn sclerosis is compatible with an involvement of the amygdala in secondary epileptogenesis.     

Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study

PURPOSE: We compare the combination of orchiectomy and radiotherapy to radiotherapy alone as treatment for pelvic confined prostate cancer, that is T1-4, pN0-3, M0 (TNM classification). MATERIALS AND METHODS: In this prospective study 91 patients with clinically localized prostate cancer were, after surgical lymph node staging, randomized to receive definitive external beam radiotherapy (46) or combined orchiectomy and radiotherapy (45). Patients treated with radiotherapy alone had androgen ablation at clinical disease progression. The effects on progression-free, disease specific and overall survival rates were calculated. RESULTS: After a median followup of 9.3 years (range 6.0 to 11.4) clinical progression was seen in 61% of the radiotherapy only patients (group 1) and in 31% of the combined treatment patients (group 2) (p = 0.005). The mortality was 61 and 38% (p = 0.02), and cause specific mortality was 44 and 27%, respectively (p = 0.06), in groups 1 and 2. The differences in favor of combined treatment were mainly caused by lymph node positive tumors. For node negative tumors there was no significant difference in survival rates. CONCLUSIONS: The progression-free, disease specific and overall survival rates for patients with prostate cancer and pelvic lymph node involvement are significantly better after combined androgen ablation and radiotherapy than after radiotherapy alone. These results strongly suggest that early androgen deprivation is better than deferred endocrine treatment for these patients.     

Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis. A randomized prospective study. Members of the Lung Study Group

Calcium (Ca) stimulates proliferation of osteoblasts in vitro, an effect proposed to be mediated by IGF I. Addition of 1 mM Ca or of 1 nM IGF I to the medium (0.3 mM Ca) of a rat bone-derived cell line, PyMS, stimulated not only DNA synthesis but also sodium-dependent (Nad) phosphate (Pi) uptake, the latter, within 2 h. These cells barely express and produce IGF I. IGF binding protein-3 which inhibits IGF action decreased neither basal nor Ca-stimulated but IGF I-stimulated NadPi transport and DNA synthesis, indicating that Ca stimulated NadPi transport and DNA synthesis independently of IGF I. The effects of Ca and IGF I on DNA synthesis were additive. 1 microM nifedipine blocked IGF I- and Ca-stimulated DNA synthesis but not NadPi transport, suggesting that Ca influx is not mediating the NadPi transport-enhancing IGF I signal but is required for IGF I-induced osteoblast proliferation.