Biomedical subjects

Russel C Huang

Publications and source records attributed to Russel C Huang.

At least 19 recordsLinked to original sources

PubMed2006

Measurement error of lumbar total disc replacement range of motion.

STUDY DESIGN: A retrospective review of lumbar total disc replacement (TDR) radiographs. OBJECTIVE: To determine the error and variability in measuring TDR radiographic range of motion (ROM). SUMMARY OF BACKGROUND DATA: Motion preservation is the driving force behind lumbar TDR technology. In the recent literature, sagittal radiographic TDR ROM as low as 2 degrees has been reported. In these studies, ROM was determined by using the Cobb method to measure TDR sagittal alignment angles in flexion-extension lateral radiographs. However, previous studies in the spinal deformity literature have shown that the Cobb method is very susceptible to measurement error. METHODS: There were 5 observers, including 2 attending orthopedic spine surgeons, 1 spine fellow, 1 fifth-year resident, and 1 fourth-year resident, who measured the ROM of 50 ProDisc II (Synthes Spine Solutions, New York, NY) TDRs on standard flexion-extension lumbar spine radiograph sets. Repeated measurements were made on 2 occasions using the Cobb method. Measurement variability was calculated using 3 statistical methods. RESULTS: The 3 statistical methods resulted in extremely similar values for TDR ROM observer variability. Overall, the intraobserver variability of TDR ROM measurement was +/-4.6 degrees, and interobserver variability was +/-5.2 degrees . CONCLUSIONS: To be 95% certain that an implanted TDR prosthesis has any sagittal motion, a ROM of at least 4.6 degrees must be observed, which is the upper limit of intraobserver measurement variability for a TDR with a true ROM of 0 degrees. To be 95% certain that a change in TDR ROM has occurred between 2 measurements by the same observer, a change in ROM of at least 9.6 degrees must be observed (the entire range of +/-4.6 degrees intraobserver variability). ROM measurement variability should be considered when evaluating the success or failure of motion preservation in lumbar TDR.

Adult↗

PubMed2006

Three-level anterior cervical discectomy and fusion with plate fixation: radiographic and clinical results.

STUDY DESIGN: Retrospective review of patients with cervical spondylosis treated with 3-level anterior cervical discectomy and fusion with plate fixation. OBJECTIVE: To assess the radiographic and clinical outcome of 3-level instrumented anterior cervical discectomy. SUMMARY OF BACKGROUND DATA: Three-level cervical discectomy without plate fixation has shown high rates of pseudarthrosis and poor outcomes. The addition of internal fixation may improve these parameters. METHODS: A total of 46 patients were observed for an average of 17.6 months (range, 6-51 months). All had 3-level anterior cervical discectomy and fusion with tricortical iliac crest autograft (4 cases), fibular ring allograft (38 cases), or titanium cage (4 cases). Allografts and cages were filled with iliac crest autograft. All patients had semirigid plating. Clinical and radiographic follow-up data were obtained. Clinical outcomes were measured as described by Robinson and with the Nurick scale. RESULTS: Forty-four patients achieved solid fusion. Two patients had additional surgery for junctional disease, and in 1 of them pseudarthrosis repair was also performed. One asymptomatic pseudarthrosis was noted. With a successful result defined as an excellent or good outcome accompanied by significant pain relief, 38 patients had a successful result (83%). Radiographic adjacent level disease was diagnosed in 11 patients after surgery and was symptomatic in 5. CONCLUSION: Three-level anterior cervical discectomy with plate fixation has a high rate of fusion, a low complication rate, and acceptable outcome in the treatment of multilevel cervical spondylosis.

Adult↗

PubMed2006

Finite element analysis of head-neck kinematics during motor vehicle accidents: analysis in multiple planes.

In this study, a detailed three-dimensional head-neck (C0-C7) finite element (FE) model developed previously based on the actual geometry of a human cadaver specimen was used. Five simulation analyses were performed to investigate the kinematic responses of the head-neck complex under rear-end, front, side, rear- and front-side impacts. Under rear-end and front impacts, it was predicted that the global and intervertebral rotations of the head-neck in the sagittal plane displayed nearly symmetric curvatures about the frontal plane. The primary sagittal rotational angles of the neck under direct front and rear-end impact conditions were higher than the primary frontal rotational angles under other side impact conditions. The analysis predicted early S-shaped and subsequent C-shaped curvatures of the head-neck complex in the sagittal plane under front and rear-end impact, and in the frontal plane under side impact. The head-neck complex flexed laterally in one direction with peak magnitude of larger than 22 degrees and a duration of about 130 ms before flexing in the opposite direction under both side and rear-side impact, compared to the corresponding values of about 15 degrees and 105 ms under front-side impact. The C0-C7 FE model has reasonably predicted the effects of impact direction in the primary sagittal and frontal segmental motion and curvatures of the head-neck complex under various impact conditions.

Accidents, Traffic↗

PubMed2006

Anterior tension band plating for anterior tibial stress fractures in high-performance female athletes: a report of 4 cases.

Stress fracture of the anterior tibial cortex is an extremely challenging fracture to treat, especially in the high-performance female athlete who requires rapid return to competition. Previous reports have not addressed treating these fractures in the world-class athlete with anterior plating. We hypothesize that anterior plating is a biomechanically sound approach to treatment of these fractures, and will lead to an earlier return to full activity than either nonoperative treatment or intramedullary nailing. We present a retrospective series of 4 case reports of 4 world-class female athletes with stress fractures of the anterior tibial cortex treated by anterior plating between 2001 and 2004. Average follow-up was 15 months (range 12 to 48 mo). Anterior tension band plating resulted in fracture healing in all 4 cases and return to full activity at a mean of 10 weeks. All patients returned to preinjury competitive levels. There were no complications of infection, nonunion, or malunion. Anterior tension-band plating of an anterior tibial stress fracture leads to rapid fracture healing and return to competition for high-performance female athletes. This approach should be considered in those athletes who wish to avoid the more prolonged convalescence associated with nonoperative treatment, or the problems, especially of the knee, associated with intramedullary nailing.

Adult↗

PubMed2006

Lumbar total disc replacement. Surgical technique.

BACKGROUND: Symptomatic lumbar degenerative disc disease is a challenging entity to treat. The results of arthrodesis may be compromised in the short term by pseudarthrosis and in the long term by pain at the iliac-crest donor site and by junctional degeneration. Total disc replacement has the potential to provide long-lasting relief to these patients. The purpose of this study was to present the clinical and radiographic results assessed seven to eleven years following a Prodisc total lumbar disc replacement. METHODS: Sixty-four patients had single or multiple-level implantation of a total lumbar disc replacement between 1990 and 1993. The mean duration of follow-up was 8.7 years. Clinical results were evaluated by assessing preoperative and postoperative lumbar pain, radiculopathy, disability, and modified Stauffer-Coventry scores. Preoperative and post-operative radiographs were evaluated by assessing preoperative and postoperative lumbar pain, radiculopathy, disability, and modified Stauffer-Coventry scores. Preoperative and post-operative radiographs were evaluated as well. Subgroup analysis was performed to determine if gender, an age of less than forty-five years, previous surgery, or multilevel surgery had an effect on outcome. RESULTS: At an average of 8.7 years post-operatively, there were significant improvements in the backpain, radiculopathy, disability, and modified Stauffer-Coventry scores. Thirty-three of the fifty-five patients with sufficient follow-up had an excellent result, eight had a good result, and fourteen had a poor result. Neither gender nor multilevel surgery affected outcome. An age of less than forty-five years and prior lumbar surgery had small but significant negative effects on outcome. Radiographs did not demonstrate loosening, migration, or mechanical failure in any patient. Five patients had approach-related complications. CONCLUSIONS: The Prodisc lumbar total disc replacement appears to be effective and safe for the treatment of symptomatic degenerative disc disease. Gender and multilevel surgery did not affect the outcomes, whereas prior lumbar surgery or an age of less than forty-five years was associated with slightly worse outcomes. Longer follow-up of this cohort of patients and randomized trials comparing disc replacement with arthrodesis are needed.

Adult↗

PubMed2005

Alendronate inhibits spine fusion in a rat model.

STUDY DESIGN: A posterolateral lumbar fusion model in rats. OBJECTIVE: To study the effects of alendronate on posterolateral lumbar fusion in rats. SUMMARY OF BACKGROUND DATA: To our knowledge, there are no studies that show a significant inhibition of manual palpation-assessed spine fusion by alendronate. METHODS: A total of 75 Sprague-Dawley rats underwent intertransverse fusion with 7-tailbone autograft at L4-L5. Animals received saline (control), alendronate equivalent to human dose (dose1, 5 microg/kg/day), or 10 times the human dose (dose10, 50 microg/kg/day) via subcutaneous osmotic pumps starting the day of surgery. Eight weeks after surgery, animals were euthanized, and fusion was assessed by manual palpation. Radiographic area and optical density of fusion masses were calculated. Histomorphometry was used to assess the percentage area of fusion masses occupied by bone or marrow tissues. RESULTS: Manual palpation fusion rates were lower in alendronate groups (50% and 40%, respectively) than in the control group (95%, P = 0.002). Interobserver and intraobserver kappa values were high (0.97-1.00). There were dose-dependent and statistically significant (P < 0.001) increases in fusion mass area and optical density with increasing alendronate dose. Fusion masses in dose10 animals had significantly higher percent area of bone tissue (P = 0.01) and lower percent area of marrow elements (P < 0.001) when compared to control animals. CONCLUSIONS: Alendronate inhibits spine fusion in rats. Fusion masses in alendronate-treated animals appeared radiographically larger and denser than those in control animals despite lower fusion rates. Quantitative histomorphometry confirmed that alendronate inhibited bone graft resorption and incorporation. We recommend that patients undergoing spine arthrodesis should not take alendronate until fusion is achieved.

Alendronate↗

PubMed2005

Accuracy of computerized frameless stereotactic image-guided pedicle screw placement into previously fused lumbar spines.

STUDY DESIGN: A retrospective chart and radiographic review of 122 pedicle screws placed with computerized stereotactic image-guidance into posterolateral fusion masses. OBJECTIVES: To determine the accuracy rate of computerized stereotactic image-guided pedicle screw placement in previously fused lumbar spines. SUMMARY OF BACKGROUND DATA: Placement of pedicle screws into a previously fused lumbar spine is challenging. The normal anatomic landmarks used to determine the starting point and trajectory of the screws have either been removed or are obscured by the fusion mass. Computerized frameless stereotaxis provides precise intraoperative real time multiplanar image-guidance and may be valuable in this clinical situation. METHODS: Computerized frameless stereotactic image-guidance was used to place pedicle screws into 78 consecutive patients with prior lumbar spine fusions. Postoperative computed tomography was available on 35 patients (231 screws). One hundred and twenty-two screws were placed into fusion masses. Pedicle cortical perforations were characterized by the direction (medial, inferior, lateral, or superior) and magnitude (in 2-mm increments) of perforation. RESULTS: Five (4.1%) of the 122 pedicle screws placed into previously fused levels were found to have unintentional cortical violations. There were 1 superior (<2 mm), 1 medial (<2 mm), and 3 lateral perforations (<2, 4, and 6 mm). None of these perforations led to clinically apparent radicular pain or weakness. No pedicle screws required revision for malpositioning. CONCLUSIONS: The accuracy rate of stereotactic image-guided pedicle screw placement into previously fused lumbar spine levels is 96%. Computerized stereotactic image-guidance may have particular application in situations in which posterior element anatomy is altered, such as in the presence of a prior fusion mass.

Adult↗

PubMed2005

Correlation between range of motion and outcome after lumbar total disc replacement: 8.6-year follow-up.

STUDY DESIGN: Retrospective radiographic and chart review. OBJECTIVE: To examine the relationship between lumbar total disc replacement (TDR) range of motion (ROM) and clinical outcome at 8.6-year follow-up. SUMMARY OF BACKGROUND DATA: There are no studies on the relationship between TDR motion and clinical outcomes. METHODS: We reviewed 38 patients who underwent 1 or 2-level TDR implantation with 51 TDR. Flexion-extension ROM was measured on lateral radiographs. Clinical outcomes were measured at 8.6 years by modified Stauffer-Coventry scores, Oswestry Disability Questionnaires (ODQ), and subjective ratings of back pain, leg pain, and disability. Spearman rank correlation coefficient was used to determine if ROM was correlated with clinical outcome. Patients were divided into 2 groups by motion (< or = 5 degrees and > 5 degrees ). Statistical differences in outcome were sought. RESULTS: Spearman rank correlation coefficient revealed weak-to-moderate but statistically significant associations between ROM and outcome for postoperative back pain (r = -0.35, P = 0.034), ODQ (r = -0.33, P = 0.046), and modified Stauffer-Coventry scores (r = 0.42, P = 0.0095). Patients with motion of > 5 degrees had superior outcomes in ODQ (mean difference 12.6 points, P = 0.026) and Stauffer-Coventry scores (mean difference 2.2 points, P = 0.015). CONCLUSIONS: The radiographic ROM at 8.6-year follow-up was positively correlated with several outcomes measures. Patients with motion > 5 degrees had clinically modest but statistically better outcomes in ODQ and modifiedStauffer-Coventry scores. Longer follow-ups will be necessary to measure fully the impact of TDR ROM on outcome.

Adult↗

PubMed2005

Advantages and disadvantages of nonfusion technology in spine surgery.

Nonfusion technology in spine surgery may improve outcomes by reducing surgical morbidity and the incidence of adjacent level degeneration; however, new technologies also introduce new short- and long-term complications. There is currently no evidence that nonfusion implants are superior to fusion in mid- to long-term follow-up. Understanding the potential risks and benefits of nonfusion technology is essential for spine surgeons and their patients. This article reviews the current evidence relating to the potential risks and benefits of nonfusion technology in spine surgery.

Arthroplasty, Replacement↗

PubMed2005

Biomechanics of nonfusion implants.

Although spine fusion is a versatile and effective technique in the treatment of spinal disorders, increased stresses on adjacent unfused levels lead to symptomatic adjacent level degeneration in many patients. The goal of nonfusion devices in spine surgery is to ablate or unload painful structures while preserving segmental motion. The intended performance of nonfusion devices such as disc replacement, nucleus pulposus replacement, and posterior stabilization devices can be understood from the biomechanics of the functional spinal unit in health and disease and the interplay between the motion segment and the device. Implant design issues can also markedly affect performance.

Animals↗

PubMed2005

Lumbar total disc replacement part I: rationale, biomechanics, and implant types.

Lumbar total disc replacement is an evolving new technology designed to preserve motion and to perhaps supplant fusion as the current "gold standard" surgical treatment for lumbar degenerative disc disease. Given the intense interest in disc replacement as a paradigm shift from fusion, this article describes the anatomy, physiology, and biomechanics of degenerative disc disease. Various treatment options and their outcomes are reviewed. A brief history of disc replacement surgery is outlined, current indications and commonly accepted contraindications for disc replacement surgery are explained, and current implants likely to be available in the United States are described. An overview of the surgical procedure is provided, with technical tips and pitfalls included. Finally, a standard postoperative regime is described.

Arthroplasty, Replacement↗

PubMed2005

Lumbar total disc replacement. Seven to eleven-year follow-up.

BACKGROUND: Symptomatic lumbar degenerative disc disease is a challenging entity to treat. The results of arthrodesis may be compromised in the short term by pseudarthrosis and in the long term by pain at the iliac-crest donor site and by junctional degeneration. Total disc replacement has the potential to provide long-lasting relief to these patients. The purpose of this study was to present the clinical and radiographic results assessed seven to eleven years following a Prodisc total lumbar disc replacement. METHODS: Sixty-four patients had single or multiple-level implantation of a total lumbar disc replacement between 1990 and 1993. The mean duration of follow-up was 8.7 years. Clinical results were evaluated by assessing preoperative and postoperative lumbar pain, radiculopathy, disability, and modified Stauffer-Coventry scores. Preoperative and postoperative radiographs were evaluated as well. Subgroup analysis was performed to determine if gender, an age of less than forty-five years, previous surgery, or multilevel surgery had an effect on outcome. RESULTS: At an average of 8.7 years postoperatively, there were significant improvements in the back-pain, radiculopathy, disability, and modified Stauffer-Coventry scores. Thirty-three of the fifty-five patients with sufficient follow-up had an excellent result, eight had a good result, and fourteen had a poor result. Neither gender nor multilevel surgery affected outcome. An age of less than forty-five years and prior lumbar surgery had small but significant negative effects on outcome. Radiographs did not demonstrate loosening, migration, or mechanical failure in any patient. Five patients had approach-related complications. CONCLUSIONS: The Prodisc lumbar total disc replacement appears to be effective and safe for the treatment of symptomatic degenerative disc disease. Gender and multilevel surgery did not affect the outcomes, whereas prior lumbar surgery or an age of less than forty-five years was associated with slightly worse outcomes. Longer follow-up of this cohort of patients and randomized trials comparing disc replacement with arthrodesis are needed.

Adult↗

PubMed2005

Measurement of total disc replacement radiographic range of motion: a comparison of two techniques.

OBJECTIVE: Current methods used to measure total disc replacement (TDR) radiographic range of motion (ROM) have not been previously evaluated. Sagittal ROM is measured by determining the change in the Cobb angle of the prosthesis from the flexion to the extension radiographs. Either the metallic endplates or the keels of the TDR prosthesis can be used as radiographic landmarks in measuring ROM. We hypothesized that use of the prosthesis keels as radiographic landmarks, when compared with the use of prosthesis endplates, might lead to more precise measurements of TDR sagittal ROM. METHODS: Two observers (a fifth-year orthopedics resident and an attending orthopedic spine surgeon) measured the ROM of 51 Prodisc II TDRs on standard flexion and extension lumbar spine radiograph sets. Repeated measurements were made on two occasions using either the keels or the endplates as landmarks. Precision was defined as the mean of the absolute differences between measurements. RESULTS: For observer A, the mean absolute difference between two measurements was 1.4 degrees with the keel method compared with 3.0 degrees with the endplate method (P < 0.001). For observer B, the mean absolute difference between two measurements was 1.8 degrees with the keel method and 3.3 degrees with the endplate method (P < 0.001). When the interobserver differences were examined, the mean absolute difference was 1.8 degrees with the keel method and 3.3 degrees with the endplate method (P < 0.001). CONCLUSIONS: Our results show that the use of TDR prosthesis keels as radiographic landmarks, when compared with the use of prosthesis endplates, yields greater precision in ROM measurement. For TDR prostheses with a keel, we recommend using the keel to measure ROM.

Adult↗

PubMed2004

The prevalence of contraindications to total disc replacement in a cohort of lumbar surgical patients.

STUDY DESIGN: This is a retrospective review of the epidemiology of contraindications to lumbar total disc replacement (TDR). OBJECTIVE: To define the prevalence of contraindications to lumbar total disc replacement in a cohort of patients undergoing lumbar surgery in the senior author's (F.P.C.) practice. SUMMARY OF BACKGROUND DATA: No published reports have documented the prevalence of contraindications to lumbar total disc replacement. METHODS: We performed a retrospective review of 100 consecutive patients who had lumbar surgery by one surgeon between September and December 2002. Procedures performed and contraindications to TDR were recorded. Contraindications to TDR included central or lateral recess stenosis, facet arthrosis, spondylolysis or spondylolisthesis, herniated nucleus pulposus with radiculopathy, scoliosis, osteoporosis, and postsurgical pseudarthrosis or deficiency of posterior elements. Patients were divided into fusion and nonfusion groups. The percentage of patients without contraindications to TDR was calculated. RESULTS: Of 100 patients, 56 had fusions and 44 had nonfusion surgery. In the fusion group, 56 of 56 patients had contraindications to TDR. In the nonfusion group, 11% (5 of 44) were candidates for TDR. Overall, 5% of patients in this series were candidates for TDR. The average number of contraindications to TDR was 2.48 (range, 0-5). CONCLUSIONS: Predictions that TDR will replace fusion are premature. A small percentage (5%) of the patients currently indicated for lumbar surgery at our institution have no contraindications to TDR. Future growth in TDR implantation will result from the indication of patients for surgery who would not be indicated today or from the elimination of current contraindications.

Adult↗

PubMed2004

Scheuermann kyphosis: safe and effective surgical treatment using multisegmental instrumentation.

STUDY DESIGN: A retrospective review was conducted on 23 consecutive patients who underwent surgical correction of Scheuermann kyphosis using modern multisegmental instrumentation. OBJECTIVE: To evaluate Scheuermann kyphosis correction and complication rates. SUMMARY OF BACKGROUND DATA: The surgical treatment of Scheuermann kyphosis remains a topic of debate. The literature of the 70s and 80s on the surgical management of this disorder using Harrington instrumentation demonstrated that operative correction is quite effective but associated with significant complications. This literature, however, may be less applicable to current clinical situations. The use of modern multisegmental instrumentation and increased awareness of potential complications may decrease the risks of current operative treatment. METHODS: Hospital charts, office charts, and radiographs on 23 consecutive patients who underwent operative treatment using multisegmental instrumentation for Scheuermann kyphosis were reviewed to identify complications of surgery. Complications were classified as minor, major, or life threatening. RESULTS: The mean follow-up was 38 months (range 10-123 months). Preoperative kyphosis ranged from 63 degrees to 104 degrees with an average of 83 degrees. Twenty of the 23 patients (87%) underwent combined anterior release/arthrodesis with posterior arthrodesis/multisegmental instrumentation. The remaining 3 patients underwent posterior arthrodesis/multisegmental instrumentation. Postoperative total kyphosis ranged from 32 degrees to 67 degrees with an average of 46 degrees. At final follow-up, the total kyphosis ranged from 37 degrees to 75 degrees with an average of 51 degrees. Overall, we had 43% minor complications, 17% major complications, and 0% life-threatening complications. CONCLUSIONS: Surgical correction of Scheuermann kyphosis can be performed safely and effectively using modern multisegmental instrumentation.

Adolescent↗

PubMed2004

Cervical epidural abscess after epidural steroid injection.

STUDY DESIGN: This is a case report of a cervical epidural abscess presenting with neurologic deficits after cervical epidural steroid injection. OBJECTIVE: To describe the presentation, diagnosis, treatment, and outcome of a rare complication of cervical epidural steroid injection. SUMMARY OF BACKGROUND DATA: Cervical epidural steroid injections are a commonly used modality in the treatment of cervical spine disease. Serious complications from the procedure are rare. There is only one previously reported case of cervical epidural abscess after cervical epidural injection in the literature. MATERIALS AND METHODS: A case of cervical epidural abscess after epidural steroid injection is presented and the relevant literature is reviewed. RESULTS: The patient had partial recovery of neurologic function within the first 24 hours after decompressive laminectomy, irrigation, and debridement. There were no perioperative complications. Intraoperative cultures permitted positive identification of the infecting organism and appropriate antibiotic selection. At 7-month follow-up, there was no recurrence of infection and the patient had recovered baseline neurologic function and neck pain status. CONCLUSIONS: Cervical epidural abscess is a rare but potentially devastating complication after epidural steroid injection. Neurologic compromise may occur. Timely diagnosis and appropriate treatment may result in good clinical outcomes.

Cervical Vertebrae↗

PubMed2004

The current status of lumbar total disc replacement.

Total disc replacement is an exciting technology that may one day replace fusion as the gold standard treatment for DDD, but it is currently an experimental procedure in the United States. Promising short- and mid-term results have been reported for TDR, but longer follow-up and randomized trials comparing TDR to fusion and nonsurgical treatment are needed to fully define the role of TDR in the spine surgeon's armamentarium. Short-term complication rates have been acceptably low, but in the long term the durability of TDR implants and the vertebral endplate will provide challenges. Finally, it is essential that practitioners understand that a limited subset of patients are good candidates for TDR and that indiscriminate application of this technology will result in poor outcomes.

Biomechanical Phenomena↗

PubMed2004

High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model.

The effect of alendronate on osteoclast and osteoblast function was studied in a novel spine pseudarthrosis model in rats. Sixty-three Sprague-Dawley rats were divided into three groups: control group (saline), therapeutic dose group (1 microg/kg/week), and one-log overdose group (10 microg/kg/week). Animals had L4-L5 posterior intertransverse process fusion with limited bone graft and were sacrificed at 2, 4, and 6 weeks. Manual palpation showed no notable differences among groups. Treatment group radiographic scores were equal to or better than control group scores and were higher than the overdose group at 2 and 6 weeks. Qualitatively, limited histologic remodeling and poor osteoclastic and osteoblastic function were noted in the alendronate treated groups. Quantitative histologic analysis showed fewer osteoclasts in the therapeutic and high-dose groups (p < 0.001). The percent osteoblasts per bone surface area was lower in the high-dose group (p < 0.05). The results suggest that the effect of alendronate was dose dependent and animal model dependent and that supranormal doses of alendronate had a deleterious effect on osteoclastic and osteoblastic function in this model.

Alendronate↗