In the treatment of spinal cord tumors, complete tumor resection with complete reconstruction of the spine represents the ideal goal. However, for the treatment of heavily calcified spinal meningioma, en-bloc resection of the tumor together with the involved dura at the tumor base through laminectomy is quite difficult. Conventional laminectomy is not wide enough to allow full exposure of such tumors, and postoperative dural defects can cause serious complications.
A 58-year-old Japanese woman presented with a 3-month history of progressive muscle weakness and numbness of the lower extremities. Magnetic resonance imaging (MRI) and computed tomography showed a calcified spinal cord tumor with dural tail sign at the T10-T11 level, severely compressing the spinal cord anterolaterally. The patient underwent en-bloc resection of the tumor with the inner layer of the dura and preservation of the outer layer of the dura through recapping T-saw laminoplasty of T10-T11, including bilateral facet joints. The tumor was histologically diagnosed as meningioma. Postoperatively, the patient achieved complete recovery of neurological functions. Bone union after laminoplasty was obtained within 6 months. Follow-up MRI at 5 years postoperatively demonstrated no recurrence of the tumor.
Resection of spinal meningioma with only the inner layer of dura can minimize postoperative complications, including spinal fluid leakage. Recapping T-saw laminoplasty provides extensive exposure for tumor removal. The combination of these techniques may offer an ideal surgical option for complete resection of spinal meningioma with complete preservation of the posterior spinal elements.
Bone union; Dural layer; Recapping laminoplasty; Spinal meningioma; T-saw
To evaluate clinical and radiological results of transforaminal lumbar interbody fusion (TLIF) performed with cortical bone trajectory (CBT) pedicle screw insertion with those of TLIF using 'conventional' or percutaneous pedicle screw insertion.
Overview of Literature
CBT is a new trajectory for pedicle screw insertion in the lumbar spine; clinical and radiological results of TLIF using pedicle screws inserted with CBT are unclear.
In total, 26 patients (11 males, 15 females) were enrolled in this retrospective study and divided into three groups: TLIF with pedicle screw insertion by conventional minimally invasive methods via the Wiltse approach (M-TLIF, n=10), TLIF with percutaneous pedicle screw insertion (P-TLIF, n=6), and TLIF with pedicle screw insertion with CBT (CBT-TLIF, n=10). Surgical results and preand postoperative radiological findings were evaluated and compared.
Intraoperative blood loss was significantly less with CBT-TLIF (p=0.03) than with M-TLIF. Postoperative lordotic angles did not differ significantly among the three groups. Complete fusions were obtained in 10 of 12 levels (83%) with M-TLIF, in seven levels (100%) with P-TLIF, and in 10 of 11 levels (91%) with CBT-TLIF. On postoperative computed tomography, correct positioning was seen in 84.1% of M-TLIF screws, 88.5% of P-TLIF screws, and 90% of CBT-TLIF screws.
CBT-TLIF resulted in less blood loss and a shorter operative duration than M-TLIF or P-TLIF. Postoperative rates of bone union, maintenance of lordotic angles, and accuracy of pedicle screw positions were similar among the three groups.
Transforaminal lumbar interbody fusion; Cortical bone trajectory; Conventional trajectory; Percutaneous insertion; Computed tomography
In surgical treatment for atypical femoral fractures (AFFs), reconstruction nail fixation is recommended for both complete and incomplete fractures. Although it has been reported that AFF is affected by many factors, The ASBMR Task Force 2013 Revised Case Definition of AFFs states that a curved femur is often seen in Asian patients. It is sometimes difficult to insert a nail into a femur in incomplete AFF patients with severely curved femurs. We report two incomplete bisphosphonate-related AFF patients with marked femoral curvatures treated by locking plates and teriparatide, showing early bone unions and favorable long-term outcomes.
Gas gangrene is most often caused by Clostridium perfringens infection. Gas gangrene is a medical emergency that develops suddenly. The mortality rate is higher with trunk involvement than with involvement of the extremities, which carries a better prognosis. With respect to vertebral involvement, there are few reports in the literature. The purpose of this paper is to report a very rare case of vertebral osteomyelitis caused by gas gangrene.
A 78-year-old Japanese woman with diabetes mellitus was admitted to our hospital with the chief complaints of back pain, dysuria, and complete paralysis of both legs. A computed tomography scan showed soft tissue swelling anterolaterally at intervertebral disc level T11/12 and a gas-containing epidural abscess that compressed her spinal cord. Cultures later grew Clostridium perfringens and Escherichia coli. Hemilaminectomy was done from T10 to T12, and an epidural abscess was removed. She went on to have fusion surgery 6 weeks after the initial operation and subsequently experienced complete pain relief. She was discharged 2 months later, at which time she was able to walk with a cane. Examination 18 months after surgery showed normal gait without a cane.
Discitis caused by gas gangrene infection was successfully treated by immediate debridement and subsequent fusion surgery.
Clostridium perfringens; Debridement; Epidural abscess; Fusion surgery; Gas gangrene; Vertebral osteomyelitis
Remote cerebellar hemorrhage is a rare complication of spinal surgery. Although loss of cerebrospinal fluid seems to play an important role in the pathogenesis of this complication, the detailed mechanism of remote cerebellar hemorrhage after spinal surgery remains unclear. We report the case of a patient with remote cerebellar hemorrhage following thoracic spinal surgery of an intradural extramedullary tumor and discuss this entity with reference to the literature.
A 57-year-old Japanese woman presented to our hospital with back pain, dysuria, and numbness of both legs. A neurological examination was performed, and imaging was performed with ordinary radiography, magnetic resonance imaging, and computed tomography. Her magnetic resonance imaging scan showed an intradural extramedullary tumor at the T3 level. A tumor resection and T1-T5 pedicle screw fixation were performed. Twelve hours after spinal surgery, she complained of unexpected dizziness, nausea, and vomiting. A total of 850mL of serosanguineous fluid had been drained at that time, and drainage was stopped. An urgent brain computed tomography scan showed a cerebellar hemorrhage. She was treated conservatively, and was able to leave hospital six weeks after the initial operation, without any neurological deficits except for slight ataxia.
Remote cerebellar hemorrhage has to be suspected when unexpected neurological signs occur after spinal surgery. If an excessive amount of cerebrospinal fluid drains from the drainage tube after spinal surgery, drainage should be stopped.
Postoperative complication; Intradural extramedullary tumor; Remote cerebellar hemorrhage; Spinal surgery; Thoracic spine; Neurological signs
A retrospective study.
To compare clinical and radiological outcomes between bilateral C2 pedicle screwing (C2PS) and unilateral C2PS, combined with contralateral C2 laminar screwing (LS), for posterior atlantoaxial fixation.
Overview of Literature
Posterior fixation with C1 lateral mass screwing (C1LMS) and C2PS (C1LMS-C2PS method) is an accepted procedure for rigid atlantoaxial stabilization. However, conventional bilateral C2PS is not always allowed in this method due to anatomical variations of C2 pedicles and/or asymmetry of the vertebral artery. Although unilateral C2PS plus contralateral LS (C2PS+LS) is an alternative in such cases, the efficacy of this procedure has not been evaluated in controlled studies (i.e., with bilateral C2PS as a control).
Clinical and radiological records of patients who underwent the C1LMS-C2PS method, using unilateral C2PS+LS (n=9), and those treated using conventional bilateral C2PS (n=10) were compared, with a minimum two years follow-up.
Postoperative complications related to the unilateral C2PS+LS technique included one case of spontaneous spinous process fracture of C2. A C1 anterior arch fracture occurred after a fall in one patient, who underwent bilateral C2PS and C1 laminectomy. No significant differences were seen between the groups in reduction of neck pain after surgery or improvement of neurological status, as evaluated using the Japanese Orthopaedic Association score. A delayed union occurred in one patient each of the groups, with the final fusion rate being 100% in both groups.
Clinical and radiological outcomes of unilateral C2PS+LS were comparable with those of the bilateral C2PS fixation technique for the C1LMS-C2PS method.
Cervical spine; Atlantoaxial instability; Laminar screw; Pedicle screw
With the population and proportion of the elderly increasing each year, difficulties with postoperative treatment outcomes after osteoporotic hip fracture are increasing. This study focused on activities of daily living (ADL) in patients who underwent surgery for hip fracture through an investigation of living arrangements, the presence of dementia, and other complications of aging. Information from 99 patients who lived either at home or in geriatric health service facilities was collected for this trial. Most patients were over 65 years of age and female, and about half of them had dementia. The postoperative ADL score (focusing on patients’ walking ability) was significant for those living at home than for those living in facilities. In addition, patients with dementia were divided into the following two categories: an early-rising group, comprising patients who were able to use a wheelchair within 48 hours of their operation; and a late-rising group, who did not start using a wheelchair until more than 48 hours after surgery. The ADL scores for the two groups were compared. Although the preoperative ADL scores were not significantly different between the two groups, postoperative ADL scores were significantly higher in the early-rising group than in the late-rising group, especially in patients who had undergone hemiarthroplasty. These data suggest that ADL in dementia patients following hip fracture depends on the surgical procedure performed and whether they are late or early risers after surgery.
delirium; dementia; rehabilitation; elderly
Anomalies in the craniovertebral junction may be a rare cause of syncope. The mechanisms of syncope related to craniovertebral junction anomaly remain unknown.
We present an extremely rare case with anomaly in the craniovertebral junction and syncope, and discuss the mechanism of the syncope.
A 10-year-old Japanese boy with a congenital anomaly in the craniovertebral junction presented with recurrent syncope. A physical examination showed generalized hyperreflexia, but motor and sensory examinations were normal. Computed tomography and magnetic resonance imaging showed basilar invagination and spinal cord compression at his craniovertebral junction. Three-dimensional computed tomography angiography revealed an anomalous course of his bilateral vertebral arteries, both of which showed a persistent first intersegmental artery that entered the spinal canal at the caudal portion of the C1 posterior arch. In this case, the arteries were nearly pinched between the C1 posterior arch and the pars interarticularis of the C2. C1 laminectomy and occiput-cervical fusion (O-C2) was performed using an instrumentation system. After surgery, the syncope was not observed.
Syncope can be related to compression of extracranial arteries within the neck. In this case, transient brain ischemia caused by the anomalous course of vertebral arteries that were pinched between the C1 posterior arch and the pars interarticularis of C2 in cervical motion was the suspected cause of the syncope.
Craniovertebral junction; Syncope; Vertebral artery
Gossypiboma is rare and mostly asymptomatic in chronic cases. It can be confused with other soft tissue masses.
Our patient was an 87-year-old Japanese man with a history of surgery for a lumbar lesion causing lumbar canal stenosis 19 years earlier. Computed tomography showed a soft tissue mass with osteolysis and periosteal thickening of the vertebral lamina. On magnetic resonance imaging, the mass showed heterogeneous signal intensity on T2-weighted imaging, suggesting a malignancy. At the time of biopsy, small pieces of retained surgical sponge were collected. Surgical treatment was performed to excise the soft tissue tumour.
Gossypiboma should be included in the differential diagnosis of soft tissue masses in the paraspinal region in patients with a history of previous spinal surgery.
Foreign body; Gossypiboma; Laminectomy; Malignant spinal tumour; Retained surgical sponge; Spinal surgery
Alagille syndrome is a multisystem disorder, which is characterized by hypoplasia of the intrahepatic bile ducts, malformations of the cardiovascular system, eyes, and vertebral column, and abnormal facies. Several of the characteristics of Alagille syndrome may result in an especially high risk of fracture. The majority of patients suffer from chronic cholestasis, which can have a variety of adverse effects on bone metabolism. In Alagille syndrome, fractures primarily occur in the lower limb long bones in the absence of significant trauma.
A 9-year-old Japanese girl with Alagille syndrome was admitted to our institution with marked hyperbilirubinemia and a pathological fracture of the femur. She had been diagnosed with biliary atresia at the age of 1 month and treated with surgical bile duct reconstruction, vitamins D and K, and ursodeoxycholic acid. However, her liver dysfunction and hyperbilirubinemia worsened. The pathological fracture of the femur was treated with low-intensity pulsed ultrasound stimulation (LIPUS) and an Ilizarov ring fixator. Seventy-four days after surgery, the patient had anatomically and functionally recovered. There was no leg-length discrepancy and no angular malalignment of the lower extremities as measured clinically and radiographically. The range of motion of the hip, knee, and ankle of the patient’s operative leg matched the range of motion in the nonoperative leg.
To the best of our knowledge, there are no reports on use of the Ilizarov frame and LIPUS in diaphyseal femoral fractures in Alagille syndrome. This case report provides evidence that this procedure is successful for managing such diaphyseal fractures in Alagille syndrome.
Alagille syndrome; Low-intensity pulsed ultrasound stimulation (LIPUS); Ilizarov ring fixator
Knee specimens of two osteoporotic patients who underwent unilateral knee arthroplasty for suspected osteonecrosis of the knee were examined histologically. Preoperative findings of magnetic resonance images in both patients were consistent with the diagnosis of osteonecrosis of the medial femoral condyles, although plain X-rays showed minimal degenerative changes. In both patients, preoperative bone mineral densities of the femoral condyle and proximal tibia of the affected side were lower than those of the unaffected side. Pathological examination of the resected femoral condyle and proximal tibia showed almost intact joint cartilage, healing of the collapsed subchondral bone, and significant trabecular bone loss. Histologically, no evidence of osteonecrosis, including empty lacunae of the trabecular bone, was observed. These findings indicated that subchondral bone collapse caused by osteoporosis, but not osteonecrosis, initiated the osteoarthritic change of the affected knee. This report emphasizes that there may be cases of progressive local osteoarthritis caused by fracture of subchondral bone because of osteoporosis.
Low-intensity pulsed ultrasound is a pain-free therapy performed daily at home by the patient and has been shown to promote fracture healing. Teriparatide is a parathyroid hormone preparation that activates osteoblastic bone formation and is also reported to be effective in promoting bony union.
We report the case of a 56-year-old Japanese male with a femoral shaft fracture who underwent intramedullary osteosynthesis nailing initially. He had no radiologic or clinical sign of healing 3 months later and low-intensity pulsed ultrasound was initiated at that time. He was reassessed in another 3 months, with evidence of mild bone consolidation but the fracture gap persisted. Subsequent treatment with human parathyroid hormone was initiated in combination with low-intensity pulsed ultrasound. Full fracture healing was present 6 months after beginning the combination low-intensity pulsed ultrasound and teriparatide. It is hypothesized that the potential additive effects of low-intensity pulsed ultrasound and teriparatide therapy ultimately triggered sufficient bone formation to support osseous union.
The case reported herein is a femoral shaft atrophic nonunion in which traditional interventions failed. Successful fracture healing was finally achieved with low-intensity pulsed ultrasound and teriparatide therapy. This is the first reported case of diaphyseal nonunion with deterioration of bone quality in long bones resolved with teriparatide and low-intensity pulsed ultrasound.
Teriparatide; Low-intensity pulsed ultrasound (LIPUS); Nonunion; Bone quality
Achondroplasia is a genetic disorder of bone growth. Congenital spinal stenosis is a well-known complication of this disease, but, to the best of our knowledge, no cases involving combined stenosis with congenital lumbar spinal stenosis and ossification of the ligamentum flavum in achondroplasia have been reported previously. In this report, we describe a case of a patient with congenital spinal stenosis with achondroplasia combined with ossification of the ligamentum flavum at the lumbar spine, which we treated with decompressive surgery.
A 75-year-old Japanese woman with achondroplasia was unable to walk due to a neurological deficit of the lower extremities caused by congenital spinal stenosis that resulted from achondroplasia and ossification of the ligamentum flavum at the lumbar spine. Congenital spinal stenosis was observed from L1 to L5, and ossification of the ligamentum flavum was identified from L1/2 to L3/4. A decompressive laminectomy from L1 to L5 and removal of the ossification of the ligamentum flavum were performed. The patient’s neurological symptoms improved after surgery. She could walk with T-cane at the time of her four-year follow-up examination.
In this report, we describe what is, to the best of our knowledge, the first known published case of ossification of the ligamentum flavum in congenital spinal stenosis associated with achondroplasia at the lumbar spine. Although resection of the ossification of the ligamentum flavum at the congenital spinal stenosis at the lumbar spine was technically difficult because of congenital narrowing of the spinal canal, thickening of the lamina and adhesion of the ossified ligamentum flavum, a wide laminectomy and resection of the ossification of the ligamentum flavum resulted in acceptable improvement of the patient’s neurological symptoms.
Achondroplasia; Lumbar spinal stenosis; Ossification of the ligamentum flavum
There has been only one reported case of neuromuscular scoliosis following chronic inflammatory demyelinating polyneuropathy (CIDP). However, no cases of scoliosis that were treated with surgery secondary to CIDP have been previously described. A 16-year-old boy with CIDP was consultant due to the progression of scoliosis with the coronal curve of 86° from T8 to T12. Posterior correction and fusion with segmental pedicle screws were performed under intraoperative spinal cord monitoring with transcranial electric motor-evoked potentials. Although the latency period was prolonged and amplitude was low, the potential remained stable. Coronal curve was corrected from 86° to 34° without neurological complications. We here describe scoliosis associated with CIDP, which was successfully treated with surgery under intraoperative spinal cord monitoring.
Chronic inflammatory demyelinating polyneuropathy; intraoperative spinal cord monitoring; scoliosis; transcranial electric motor-evoked potentials
Posterior epidural migration of thoracic disc herniation is extremely rare but may occur in the same manner as in the lumbar spine.
A 53-year-old Japanese man experienced sudden onset of incomplete paraplegia after lifting a heavy object. Magnetic resonance imaging revealed a posterior epidural mass compressing the spinal cord at the T9-T10 level. The patient underwent emergency surgery consisting of laminectomy at T9-T10 with right medial facetectomy, removal of the mass lesion, and posterior instrumented fusion. Histological examination of the mass lesion yielded findings consistent with sequestered disc material. His symptoms resolved, and he was able to resume walking without a cane 4 weeks after surgery.
Pre-operative diagnosis of posterior epidural migration of herniated thoracic disc based on magnetic resonance imaging alone may be overlooked, given the rarity of this pathology. However, this entity should be considered among the differential diagnoses for an enhancing posterior thoracic extradural mass.
Intervertebral disc herniation; Posterior migration; Thoracic spine
The development of a symptomatic herniated cervical disc before the age of 20 is extremely rare. Sporadically reported cases of patients with cervical disc herniation under the age of 20 usually have had underlying disease.
Case 1: A 19-year-old Asian man visited our clinic and presented with progressive pain in his upper left scapula and weakness of the left deltoid and biceps brachii muscles. C5 radiculopathy by soft disc herniation at C4-C5 without calcification was diagnosed. Microsurgical posterior foraminotomy was performed and he recovered completely eight weeks after the surgery.
Case 2: A 15-year-old Asian man presented with difficulty in lifting his arm and neck pain on the right side. Neurological examination showed weakness of the right deltoid and biceps brachii muscles. A magnetic resonance imaging scan demonstrated a herniated intervertebral disc in the right C4-C5 foramen. The patient was treated conservatively and put under observation only, and had completely recovered eight weeks after admission.
Although extremely rare, symptomatic cervical disc herniations may occur even in the younger population under the age of 20 without any trauma or underlying disease. Favorable outcomes can be achieved by conventional treatments for cervical disc herniation.
We demonstrate for the first time therapeutic effects of vitamin K2 (menatetrenone) on pregnancy-associated osteoporosis with multiple vertebral fractures in four cases. Due to its safety, vitamin K2 presents itself as a treatment option for women with pregnancy-associated osteoporosis. Desirably, future controlled studies should verify these findings.
Pregnancy-associated osteoporosis; vertebral fracture; vitamin K2
A retrospective study.
To examine the efficacy and safety for a posterior-approach circumferential decompression and shortening reconstruction with a titanium mesh cage for lumbar burst fractures.
Overview of Literature
Surgical decompression and reconstruction for severely unstable lumbar burst fractures requires an anterior or combined anteroposterior approach. Furthermore, anterior instrumentation for the lower lumbar is restricted through the presence of major vessels.
Three patients with an L1 burst fracture, one with an L3 and three with an L4 (5 men, 2 women; mean age, 65.0 years) who underwent circumferential decompression and shortening reconstruction with a titanium mesh cage through a posterior approach alone and a 4-year follow-up were evaluated regarding the clinical and radiological course.
Mean operative time was 277 minutes. Mean blood loss was 471 ml. In 6 patients, the Frankel score improved more than one grade after surgery, and the remaining patient was at Frankel E both before and after surgery. Mean preoperative visual analogue scale was 7.0, improving to 0.7 postoperatively. Local kyphosis improved from 15.7° before surgery to -11.0° after surgery. In 3 cases regarding the mid to lower lumbar patients, local kyphosis increased more than 10° by 3 months following surgery, due to subsidence of the cages. One patient developed severe tilting and subsidence of the cage, requiring additional surgery.
The results concerning this small series suggest the feasibility, efficacy, and safety of this treatment for unstable lumbar burst fractures. This technique from a posterior approach alone offers several advantages over traditional anterior or combined anteroposterior approaches.
Lumbar spine; Burst fracture; Posterior approach
This case report describes a rare case of recurrent dislocation of the patella which was accompanied with trochlear dysplasia and malalignment of the patella in a 15-year-old girl. She complained of hemoarthrosis and recurrent patellar dislocation in the early knee flexion phase. Plain radiography and computed tomography (CT) showed patellar malalignment (quadriceps angle 20°) and severe dysplasia of the trochlea of the femur (sulcus angle 170°). Surgery was performed, consisting of trochleoplasty in addition to proximal and distal realignment. Trochleoplasty was undertaken using a modified Dejour technique. After surgery, the patient complained of joint contracture. Arthroscopic release of fibrous tissue relieved symptoms and obtained normal range of motion without patellar dislocation. Postoperative radiography and CT demonstrated improvement of the quadriceps angle (10°) and sulcus angle (140°).
Dislocations; knee; patella
Although lumbar spinal stenosis (LSS) occurs almost universally with aging, little is known regarding its actual prevalence and relationships to chronic low back pain (CLBP) in the general population. The presence of CLBP in subjects with LSS may have negative impacts on spinal alignment and mobility. This study evaluated the prevalence of LSS using a self-administered, self-reported history questionnaire in 630 community-dwelling individuals ≥50 years old. Subjects with LSS were further divided into LSS+CLBP and LSS alone groups, and spinal alignment and mobility were compared using a computer-assisted device. Prevalence of LSS was 10.8% in this cohort. Subjects in the LSS+CLBP group (n = 46) showed a significantly more kyphotic lumbar spinal alignment with limited lumbar extension (P < .05), resulting in a stooped trunk compared to subjects in the LSS alone group (n = 22). However, no significant difference in spinal mobility was seen between groups.
Lower acute kyphosis (LAK) is a postural deformity caused by severe osteoporotic vertebral collapse at the thoracolumbar junction. Corrective surgery is indicated for severe cases, but no case report using a fresh-frozen femoral head allograft was found in the English literature.
A 69-year-old Japanese woman with severe LAK with osteoporotic vertebral fractures from T11 to L2 complained of severe back pain and difficulty in walking. The rigid kyphosis measured 74° from T10 to L3. The patient underwent an anterior release and interbody fusion using a fresh-frozen femoral head allograft (T11-L3) and a posterior instrumented fusion (T10-L3). Postoperatively, kyphosis was corrected to 28°, and the patient's symptoms were alleviated. The allograft bone was fully incorporated 1 year postoperatively. A new vertebral fracture at T10 occurred after 2 years, resulting in a slight loss of correction. A kyphosis angle of 35° at 2 years was maintained at 12 years (age, 81 years). She remained free of back pain and able to walk without a cane over the 12-year follow-up.
For treatment of severe osteoporotic LAK, anterior reconstruction is essential to obtain good spinal alignment and prevent recurrence. A fresh-frozen femoral head allograft, in combination with rigid posterior instrumented fixation, fulfills this function.
Recent studies support the concept that IGF-binding protein-5 (IGFBP-5) stimulates bone formation, at least in part, via IGF-independent mechanisms. To evaluate this hypothesis further, we evaluated in vitro and in vivo effects of IGFBP-5 on bone formation parameters using the IGF-I knockout (KO) mouse. Treatment of serum-free cultures of osteoblast clones derived from IGF-I KO mice with recombinant human IGFBP-5 increased both proliferation and alkaline phosphatase (ALP) activity in a dose-dependent manner, an effect comparable to that seen with IGF-I. IGF-II levels from media conditioned by osteoblasts derived from IGF-I KO mouse were below those detectable by RIA. To eliminate possible actions of IGF-II, if any was produced by osteoblasts derived from IGF-I knockout mice, the IGFBP-5 effect was studied in the presence of exogenously added IGFBP-4, a potent inhibitor of IGF-II actions in bone cells. Addition of IGFBP-4 blocked IGF-I– but not IGFBP-5–induced cell proliferation in osteoblasts derived from IGF-I knockout mice. Consistent with in vitro results, a single local injection of IGFBP-5 to the outer periosteum of the parietal bone of IGF-I KO mice increased ALP activity and osteocalcin levels of calvarial bone extracts. The magnitudes of IGFBP-5–induced increases in ALP and osteocalcin in parietal bone extracts of IGF-I KO mice were comparable to those seen in C3H mice. In contrast to IGFBP-5, local administration of IGFBP-4 had no significant effect on bone formation in C3H and IGF-I KO mice. These results provide the first direct evidence to our knowledge that IGFBP-5 functions as a growth factor that stimulates its actions in part via an IGF-independent mechanism.