Inhibition of Glial Activation in Rostral Ventromedial Medulla Attenuates Mechanical Allodynia in a Rat Model of Cancer-induced Bone Pain

Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP). Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facilitation circuitry, but so far the mechanisms are poorly known. In this study, we investigated the role of RVM glial activation in the descending nociceptive facilitation circuitry in a CIBP rat model. CIBP rats showed significant activation of microglia and astrocytes, and also up-regulation of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and pro-inflammatory mediators released by glial cells (IL-1β, IL-6, TNF-α and brain-derived neurotrophic factor) in the RVM. Stereotaxic microinjection of the glial inhibitors (minocycline and fluorocitrate) into CIBP rats’ RVM could reverse the glial activation and significantly attenuate mechanical allodynia in a time-dependent manner. RVM microinjection of p38 MAPK inhibitor (SB203580) abolished the activation of microglia, reversed the associated up-regulation of proinflammatory mediators and significantly attenuated mechanical allodynia. Taken together, these results suggest that RVM glial activation is involved in the pathogenesis of CIBP. RVM microglial p38 MAPK signaling pathway is activated and leads to the release of downstream pro-inflammatory mediators, which contribute to the descending facilitation of CIBP.

Unexplained abdominal pain due to a fish bone penetrating the gastric antrum and migrating into the neck of the pancreas: A case report

BACKGROUND Ingestion of foreign bodies results in gastrointestinal perforation in approximately 1% of patients,and fish bones are the objects that most commonly lead to bowel perforation. When it does occur,the terminal ileum is the most common site of perforation,followed by the duodenal C-loop. However,involvement of the pancreas is very rare. Because clinical symptoms are nonspecific and gastrointestinal perforation may present as only odynophagia or abdominal pain,a definite preoperative diagnosis and clinical intervention may be delayed.CASE SUMMARY We report the case of a 32-year-old man who presented to our hospital because of abdominal pain that had worsened over 5 d. He had no significant past history except that he had eaten fish 1 wk previously. Upper endoscopy revealed an irregular submucosal tumor on the front wall of the gastric antrum. Endoscopic ultrasonography and computed tomography showed a fish bone penetrating the gastric antrum and migratingin to the neck of the pancreas. The patient underwent laparoscopic surgery and had no complications one week after the operation.CONCLUSION A recent history of foreign body ingestion and imaging examinations are helpful for diagnosis of unexplained abdominal pain caused by foreign bodies.

Vertebral Bone Drilling (Puncture) Attenuates the Acute Pain Due to Vertebral Compression Fractures

Purpose: The Investigational Vertebroplasty Efficacy and Safety Trial (INVEST), a randomized blinded controlled study of Vertebroplasty, demonstrated similar improvements in pain between blinded Vertebroplasty and sham-Vertebroplasty groups. The result from the RCT study suggested that the observed efficacy of the Vertebroplasty procedure, instead of representing the cement-mediated reduction in pain, may relate to the vertebral bone drilling per se. The aim of this study was to demonstrate the effectiveness of pain relief of vertebral bone drilling at the site of painful osteoporotic vertebral compression fractures in the acute phase. Materials and Methods: Twenty-six patients with painful osteoporotic compression fractures underwent the vertebral bone drilling. We assessed primary outcome measures in the NRS pain score and RDQ score at day 0 and 3 following the drilling. Comparisons were made by using Wilcoxon signed rank test. Results: The mean baseline NRS and RDQ score, and the mean NRS and RDQ score at day 3 were 7.3 ± 1.2, 15.7 ± 4.2, 4.6 ± 1.4, 7.3 ± 2.2, respectively. Among the patients, we detected significant improvements in NRS pain score and RDQ score at day 3 following the drilling compared with day 0 (P < 0.001). Conclusion: Vertebral bone drilling at the site of painful vertebral compression fractures alleviated the intractable pain due to osteoporotic vertebral compression fractures.

Effects of Curcumin on Biological Behavior and NF-κB/TNF-α Pathway in Mice with Metastatic Bone Pain of Breast Cancer Induced by Walker 256 Cells

Background. The active ingredient curcumin of traditional Chinese medicine was selected as the research object to investigate the possible mechanism of breast cancer metastatic bone pain in mouse walker 256 cells and the effect of curcumin on the NF-κB/TNF-α pathway in order to provide a new idea for clinical treatment of breast cancer metastatic bone pain. Methods. By establishing an animal model of breast cancer bone metastasis in walker 256 cells, the biological behavior of nude mice was observed on the 8th day after successful modeling. Meanwhile, the low dose group, middle dose group and high dose group of mice were given 15 mg/kg, 25 mg/kg, 50 mg/kg of curcumin solution intraperitoneally in 21 days, and the right cavity bone and spinal cord distended in mice (L4-L6) tissues were used to detect related factors, Immunohistochemical method was used to detect c-fos in spinal cord. Expression levels of RANK, NF-κB and TNF-α were detected by RT-PCR and Western blot. Meanwhile, serum levels of Cox2, il-6, leukotriene and PGE2 were detected. Results. Observing the biological behavior index of nude mice, we found that the mechanical pain and thermal pain threshold decreased (p < 0.05), and the cold pain and spontaneous pain scores increased significantly (p < 0.05). After group study, the expression of c-fos in the cancer pain model group was significantly higher than that in the normal control group (p < 0.05), and with the increase of curcumin dose, the expression of c-fos in the high dose group was significantly lower than that in the solvent model group (p < 0.05). The expression of RANK, NF-κB, TNF-α was higher than that of the normal control group and decreased gradually with the increase of curcumin dose, among which the expression of high dose group was significantly lower than that of solvent group (p < 0.05). RANK, NF-κB, TNF-α protein expression was higher than that of normal control group and gradually decreased with the increase of curcumin dose. The levels of Cox2, IL-6, leukotriene and PGE2 in serum decreased with the increase of curcumin dose, and the high dose group decreased significantly (p < 0.05). Conclusions. On the 8th day after the success of the animal model of breast cancer bone metastasis in Walker 256 cells, abnormal biological behaviors such as heat pain, cold pain sensation and spontaneous hyperalgesia were observed. Further studies have found that the increased expression of rank on osteoclasts induced up-regulated expression of NF-κB and c-fos, induced expression of TNF-α gene, and could induce synthesis and release of leukotriene, PGE2 through direct activation of cyclooxygenase, inflammatory media IL-6 cascade reaction, resulting in pathological pain and hypersensitivity. Traditional Chinese medicine active ingredient curcumin could reduce RANK expression of osteoclast, inhibit cell NF-κB and spinal cord c-fos activity, reduce TNF-α expression, inhibit Cox2 activity, and reduce the synthesis and release of inflammatory factors leukotriene and PGE2, thus exerting its analgesic effect, which provides new ideas and methods for clinical treatment of metastatic bone pain in breast cancer.

JNK in Spinal Cord Facilitates Bone Cancer Pain in Rats through Modulation of CXCL1

In patients with advanced cancer, cancer-induced bone pain（CIBP） is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase（JNK） and chemokine（C-X-C motif） ligand 1（CXCL1） have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1（p JNK1） and p JNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective p JNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the p JNK/CXCL1 pathway may provide a new choice for treatment of CIBP.

Targeting the nitric oxide/cGMP signaling pathway to treat chronic pain

Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.

Analysis of therapeutic efficacy of Aredia in treating pain caused by advanced malignant metastatic bone tumors

Objective To study therapeutic efficacy of Aredia in treating malignant metastatic bone tumors. Method 60～90 mg Aredia was administrated iv in 31 cases with malignant metastatic tumors,once each week. Results Pain in 12 cases was significantly relieved.14 cases acquired relif.Total effective rate was 83.9%.Activity ability was improved by 80.6%.No apparent toxicological and adverse effects as well as fever and cold symptoms were observed.Conclusion Aredia is a kind of ideal drugs for treatment of pain caused by malignant metastatic bone tumors.It is convenient in use and could be endured by patients.

The associations of TMJ pain and bone characteristics on the activities of daily living

The aim of this investigation was to analyze the associations of TMJ pain/discomfort and bone characteristics on the activities of daily living in a population based study. Methods: The study included 95 randomly selected participants. The impact of temporomandibular joint pain/discomfort on the daily activeties was assessed by using the daily living scale by List and Helkimo (1995). The levels of serum type I collagen telopeptide fragments (P1NP), C-telopeptide crosslaps of type I collagen (CTX-1), and vitamin D (25 (OH) D) were analysed. The Mann-Whitney U-test, Spearman rank correlation coefficent (rs) were used for statistical analyses. Results: Activities of daily living were influenced by temporomandibular joint pain/discomfort to varying degrees. The degree of pain/discomfort during eating was correlated with the level of C-telopeptide crosslaps of type I collagen (p = 0.02) and type 1 collagen telopeptide fragments (p = 0.04). The females in the study had significantly lower vitamin D levels compared to males (p = 0.04). Conclusions: This population based study indicates that TMJ pain/discomfort exerts a significant negative influence on activities of daily living and is related to the biochemical markers of bone turnover and 25 (OH) D level. Several functions of daily activities such as social life, exercising and eating are the most disturbed.

Serum Vitamin D and Bone Mineral Density in Children with Growing Pain in a Tertiary Hospital of Bangladesh

Background:Growing pain (GP) is the most common form of nonspecific, recurrent leg pain in children aged 4 - 12 years. The exact etiology of GP is not known. However, some studies have found an association between vitamin D and Bone Mineral Status (BMD) status with GP in their study. Objectives: To assess the serum level of vitamin D, and BMD and to determine their association with growing pain in children. Methods: This cross-sectional analytical study was conducted in the Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU). Sixty children between the age of 6 - 12 years were included in the study from March 2020 to August 2021. Children who fulfilled the Evans criteria of GP were enrolled as cases and thirty age and sex matched healthy children were recruited as the control in the study. Informed written consent was obtained from patients and parents. Serum 25-hydroxy-vitamin-D levels and BMD were performed among cases and controls and subsequently compared to see their association in growing pain. A preformed semi-structured questionnaire was completed for each participant which included socio-demographic, clinical and laboratory characteristics. Appropriate statistical tests were applied for data analysis and performed by SPSS version 22. A p-value less than 0.05 was considered as significant at a 95% confidence interval. Results: In this study, 96.7% of growing pain patients had hypovitaminosis D and among them,<span style="font-family: "> the majority (86.7%) was vitamin D deficient. There was a significant association between vitamin D with GP compared to healthy control. BMD was significantly lower in the lumbar vertebra (L1 -<span style="font-family: "> L4) and femoral neck region (both right and left) among GP children compared to the control group. Conclusion: From this study, it may be concluded that the majority of children with GP had hypovitaminosis D and low BMD status compared to the control. Vitamin D deficiency and low BMD status were significantly associated with children with growing pain. Institutional Review Board (I.R.B.) Clearance Certificate (NO. BSMMU/2020/4503 Date: 15/03/2020) was provided from the office of the Registrar, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.

The effects of Yishen Qutong granula on pain sensitization and bone destruction of rats with bone cancer pain

Objective:To study the effects of Yishen Qutong granula on pain sensitization and bone destruction of rats with bone cancer pain.Methods:Walker256 cells were passaged in ascites and injected into the tibia of female Wistar rats to prepare the bone cancer pain model.On the 14th day after model establishment,60 rats were randomly divided into model group,sham-operated group,Yishen Qutong granula low,middle,high dose group and tramadol hydrochloride positive control group.After continuous administration for 14 days,the mechanical pain threshold,thermal threshold and weight-bearing difference of both hind limbs were observed.Results:Compared with the model group,Yishen Qutong groups increased the mechanical pain threshold,thermal pain threshold and reduced the weight difference of both hind limbs(P<0.05).Compared with the positive drug group,there was no significant difference in increasing the mechanical pain threshold and thermal pain threshold of rats in the medium dose group of Yishen Qutong(P>0.05),and Yishen Qutong granula significantly reduced the weight-bearing difference of hind limbs in all groups(P<0.05).Conclusion:Yishen Qutong granula can relieve pain sensitization and alleviate bone damage in rats with bone cancer pain.

Sacrum magnetic resonance imaging for low back and tail bone pain:A quality initiative to evaluate and improve imaging utility

As quality and cost effectiveness become essential in clinical practice,an evidencebased evaluation of the utility of imaging orders becomes an important consideration for radiology’s value in patient care.We report an institutional quality improvement project including a retrospective review of utility of sacrum magnetic resonance(MR)imaging for low back pain at our institution over a four-year period and follow-up results after physician education intervention.Sacral MR imaging for low back pain and tailbone pain were only positive for major findings in 2/98(2%)cases,and no major changes in patient management related to imaging findings occurred over this period,resulting in almost$500000 cost without significant patient benefit.We distributed these results to the Family Medicine department and clinics that frequently placed this order.An approximately 83%drop in ordering rate occurred over the ensuing 3 mo follow-up period.Sacrum MR imaging for low back pain and tail bone pain has not been a cost-effective diagnostic tool at our institution.Physician education was a useful tool in reducing overutilization of this study,with a remarkable drop in such studies after sharing these findings with primary care physicians at the institution.In conclusion,sacrum MR imaging rarely elucidates the cause of low back/tail pain diagnosed in a primary care setting and is even less likely to result in major changes in management.The practice can be adopted in other institutions for the benefit of their patients and improve cost efficiency.

Combined chemotherapy with Boning in the treatment of pain due to bone metasta ses from malignant tumors

Objective To investigate the effect of Boning o n pain due to bone metastases from mal ignant tumors.Method From De-cember,1998to December,2000,86pa tients with pathologically proved b one metastases from malignant tumors were randomly divided into two groups,study group(combined chemotherapy with boning),control group(simple chemotherapy).Boning(60mg )dissolved in saline solution(500ml )were given IV for consecutive 3days.Then 60mg Boning was given every half-month .Patients in control group accepted simple chemotherapy.Results Efficacy in study group was 88.37%which was significantly superior to th at in control group(66.47%).Boning could repair injured bone.Adverse r eaction associated with Boning was weak.Boning quickly relieved sympto ms for a long time.Conclusion Effect of large-dose Boning for reli eving pain due to bone metastases fro m malignant tumors is satisfying.At the same time,Boning play im-portant role in repair of destructed bone.

Clinical research on zoledronic acid in treatment of pain caused by bone metastasis of malignant tumors

Objective:To evaluate the efficacy and safety of zoledronic acid for the pain caused by metastatic tumor of bone.Methods:52 patients with metastatic tumor of bone were randomly divided into two groups.The zoledronic acid group received 4 mg zoledronic acid infusion for 30 minutes and the control group received 90 mg pamidronate infusion for 6 hours. Results:The effective rates in zoledronic acid group and control group were 73.08%and 69.23%respectively.No significant difference was observed between the two groups.The median pain relief onset at days 5 and 7,respectively,and no significant difference was observed.The ECOG scores on the 7th day after medication:the differences in the zoledronic acid group before and after medication and between the two groups were both significant(P<0.001 and P=0.0448).The adverse reac- tion was no significant difference between the two groups.Conclusion:Zoledronic acid is efficient and safe in the treatment of pain caused by metastatic tumor of bone and it has low adverse reaction rate and convenient shorter using time.

The role of radioisotopes for the palliation of bone pain flrOm bone metastases

Bone metastasis occurs as a result of a complex pathophysiologic process between host and tumor cells leading tO cellular invasion,migration adhesion,and stimulation of osteoclastic and osteoblastic activity.Several sequences occur as a result of osseous metastases and resulting bone pain Can lead to significant debilitation.Pain associated with osseous metastasis is thought to be distinct from neuropathic or inflammatory pain.Several mechanisms,such as invasion of tumor cells,spinal cord astrogliosis. and sensitization of nervous system,have been postulated to cause pain.Pharmaceutical therapy of bone pain includes nonsteroidal analgesics and opiates.These drugs are associated with side effects,and tolerance to these agents necessitates treatment with other modalities.Bisphosphonates act by inhibiting osteoclast—mediated resorption and have been increasingly used in treatment of pain- ful bone metastasis.While external beam radiation therapy remains the mainstay of pain palliation of solitary lesions,bone-seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions.32P has been used for over 3 decades in the treatment of multiple osseous metastases.The myelosuppression caused by this agent has led to the development of other bone-seeking radiopharmaceuticals.including 89SrCl.and 153Sm-ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP).89Sr is a bone-seeking radionuclide.whereas 153Sm—EDTMP is a bone—seeking tetraphosphonate;both have been approved by the Food and Drug Administration for the treatment of painful osseous metastases.While both agents have been shown to have efficacy in the treatment of painful osseous metastases from prostate cancer,they may also have utility in the treatment of painful OSSEOUS metastases from breast cancer and perhaps from non—small cell lung cancer.This article illustrates the salient features of these radiopharmaceuticals,including the approved dose,method of administration,and indications for use.

Pain relief by palliative radiotherapy in patients with advanced bone metastases

Objective: To compare 3 local field radiation therapies for bone metastases to determine the strategy producing the best results. Methods: Among 104 patients with bone metastases, 30 patients were given 8 Gy in single fraction, 31 given 20 Gy in 5 fractions, 43 given 40 Gy in 20 fractions. Results and Conclusion: The method of 40 Gy in 20 fractions had a higher pain relief rate and a lower pain relapse rate, suggesting that large-dose fractioned treatment regimen is more appropriate for patients with bone metastasis.

Effect of different hip replacement methods under minimally invasive anterolateral approach on bone metabolism and joint pain in patients with femoral neck fracture

Objective: To explore the effect of different hip replacement methods under minimally invasive anterolateral approach on bone metabolism and joint pain in patients with femoral neck fracture. Methods: A total of 110 patients with femoral neck fracture who were treated in Ruijin Hospital North, Shanghai Jiaotong University School of Medicine between July 2015 and January 2017 were collected and divided into control group and observation group by random number table, each with 55 cases. Control group accepted half hip replacement under minimally invasive anterolateral approach, and observation group accepted total hip replacement under minimally invasive anterolateral approach. The differences in contents of bone metabolism and joint pain-related indexes were compared between the two groups before and after surgery. Results: Before surgery, serum contents of bone formation indexes, bone resorption indexes, inflammatory indexes and pain mediators were not statistically significant between the two groups. 1 month after surgery, serum bone formation indexes PINP, BAP and BGP contents of observation group were higher than those of control group;serum bone resorption indexes β-CTX and TRACP-5b contents were lower than those of control group;serum inflammatory indexes IL-1 and TNF-α contents were lower than those of control group;serum pain mediators 5-HT and PGE2 contents were lower than those of control group. Conclusion: Total hip replacement under minimally invasive anterolateral approach is more effective to promote the formation of bone formation/bone resorption balance and reduce the joint pain.

Effects of p38 MAPK inhibitor on the rat pain behavior and proinflammatory cytokines in a metastatic bone cancer pain model

Objective:To observe the effects of p38 mitogen activated protein kinase(MAPK) inhibitor SB203580 by intra-thecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods:Eleven rats were used to establish the models of bone cancer pain,six rats were treated by intrathecal SB203580 injection,and the other 5 were as the controls. The paw withdrawal latency(PWL),histology and the spinal levels of IL-1β and TNF-α were detected. Results:All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However,following intrathecal injection of SB203580,the left PWLs(12.12 ± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days) were significant higher than that of controls(9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days),P < 0.05. Meanwhile,intrathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion:Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity,which might result from inhibiting intracellular p38 MAPK signaling transduction,and thereby reducing the release of the proinflammatory cytokines.

Treatment of postherpetic neuralgia by bone marrow aspirate injection:A case report

BACKGROUND Postherpetic neuralgia(PHN)is the most frequent and a difficult-to-treat complication of herpes zoster(HZ).Its symptoms include allodynia,hyperalgesia,burning,and an electric shock-like sensation stemming from the hyperexcitability of damaged neurons and varicella-zoster virus-mediated inflammatory tissue damage.HZ-related PHN has an incidence of 5%–30%,and in some patients,the pain is intolerable and can lead to insomnia or depression.In many cases,the pain is resistant to pain-relieving drugs,necessitating radical therapy.CASE SUMMARY We present the case of a patient with PHN whose pain was not cured by conventional treatments,such as analgesics,block injections,or Chinese medicines,but by bone marrow aspirate concentrate(BMAC)injection containing bone marrow mesenchymal stem cells.BMAC has already been used for joint pains.However,this is the first report on its use for PHN treatment.CONCLUSION This report reveals that bone marrow extract can be a radical therapy for PHN.

Adult-onset hypophosphatemic osteomalacia as a cause of widespread musculoskeletal pain:A retrospective case series of single center experience

BACKGROUND Osteomalacia(OM)is frequently confused with various musculoskeletal or other rheumatic diseases,especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-specific manifestations.AIM To facilitate the early diagnosis and etiology-specific treatment of adult-onset hypophosphatemic OM.METHODS A retrospective review of medical records was performed to screen adult patients who visited a physiatry locomotive medicine clinic(spine and musculoskeletal pain clinic)primarily presenting with widespread musculoskeletal pain at a single tertiary hospital between January 2011 and December 2019.We enrolled patients with hypophosphatemia,high serum bone-specific alkaline phosphatase levels,and at least one imaging finding suggestive of OM.RESULTS Eight patients with adult-onset hypophosphatemic OM were included.The back was the most common site of pain.Proximal dominant symmetric muscle weakness was observed in more than half of the patients.Bone scintigraphy was the most useful imaging modality for diagnosing OM because radiotracer uptake in OM showed characteristic patterns.Six patients were diagnosed with adefovir(ADV)-induced Fanconi syndrome,and the other two patients were diagnosed with tumor-induced OM and light-chain nephropathy,respectively.After phosphorus and vitamin D supplementation and treatment for the underlying etiologies,improvements in pain,muscle strength,and gait were observed in all patients.CONCLUSION Mechanical pain characteristics,hypophosphatemia,and distinctive bone scintigraphy patterns are the initial diagnostic indicators of adult-onset hypophosphatemic OM.ADV-induced Fanconi syndrome is the most common etiology of hypophosphatemic OM in hepatitis B virus-endemic countries.