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Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare inherited autoimmune disease, characterized by a classic triad, including chronic mucocutaneous candidiasis, primary adrenocortical insufficiency and hypoparathyroidism. The present study investigated phenotypes and pathogenic variants in a Chinese woman with non-classical APS-1. Disease-associated variants in a patient with APS-1 were identified via targeted next generation sequencing and the variant was confirmed via Sanger sequencing. Serum levels of calcium, phosphorus, parathyroid hormone (PTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and urinary levels of calcium were measured. Blood count assays and bone marrow morphology were investigated. The patient was a 32-year-old woman who had suffered from typical carpopedal spasms since she was 7 years old. She developed syncope, primary amenorrhea, intermittent diarrhea and general fatigue in subsequent years. Hypocalcemia, hyperphosphatemia, low levels of PTH and estradiol, elevated levels of FSH and LH, and absence of erythroblasts were observed, which indicated hypoparathyroidism, primary ovarian insufficiency and pure red cell aplasia. A novel heterozygous missense variant (NM_000383.2: c.623G>T, NP_000374.1: p.Gly208Val) in exon 5 of autoimmune regulator and a reported variant (NM_000383.2: c.371C>T, NP_000374.1: p.Pro124Leu) in exon 3 were detected, of which the c.623G>T variant may be a pathogenic variation that induces APS-1. Under a regular follow-up and therapeutic adjustment of calcium, calcitriol, hormone replacement therapy and methylprednisolone, the endocrine function and clinical symptoms of the patient were notably improved. The results of the present study expand the known genetic and phenotypical spectra of APS-1.

Background Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement. Methods We reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without. Results The two patients were both males with complete-form PHO for more than 10 years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of SLCO2A1 according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%, P P = 0.003), and myelofibrosis (19.0% vs. 0.9%, P = 0.002) than those without. Most patients with gastrointestinal complication had SLCO2A1 mutation (86.7%, 13 /15). Conclusions Digestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn’s disease but similar to CMUSE. Mutations in SLCO2A1 might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications.

At least 15 candidate genes have been implicated in hypoparathyroidism (HP). However, comprehensive screening of causative genes for HP is lacking. Here, we investigated the genotype spectrum in a large group of Chinese patients with childhood onset HP. A total of 173 patients with childhood onset HP were analyzed using targeted next-generation sequencing (NGS), including 15 candidate genes combined with multiplex ligation-dependent probe amplification (MLPA) of the TBX1 gene. Twenty-seven pathogenic or likely pathogenic mutations in five genes (TBX1, AIRE, GATA3, FAM111A, and CASR) including 13 novel variants in 23 patients, and 12 variants of uncertain clinical significance in five genes (GATA3, CASR, FAM111A, GCM2, and PTH) in 11 patients, were identified by NGS. Additionally, an entire gene deletion of TBX1 in 25 patients was found by TBX1-MLPA. Combined with clinical data, 26 (15.0%) cases of DiGeorge syndrome (OMIM #188400), nine (5.2%) autoimmune polyglandular syndrome type 1 (OMIM #240300), eight (4.6%) autosomal dominant hypocalcemia type 1 (OMIM #601198), four (2.3%) hypoparathyroidism-deafness-renal dysplasia syndrome (OMIM #146255), and one (0.6%) Kenny-Caffey syndrome type 2 (OMIM #127000) were verified. Among them, 16 of 26 (61.5%) DiGeorge syndrome cases were undiagnosed due to the lack of obvious clinical clues before genetic testing. The onset age of patients with mutations (median [interquartile range], 2.8 [0.1, 9.6] years) was significantly earlier than those without mutations (13.0 [8.8, 15.0] years) (p

Background:. Osteogenesis imperfecta (OI), a heritable bone fragility disorder, is mainly caused by mutations in COL1A1 gene encoding α1 chain of type I collagen. This study aimed to investigate the COL1A1 mutation spectrum and quantitatively assess the genotype-phenotype relationship in a large cohort of Chinese patients with OI. Methods:. A total of 161 patients who were diagnosed as OI in Department of Endocrinology of Peking Union Medical College Hospital from January 2010 to December 2017 were included in the study. The COL1A1 mutation spectrum was identified by next generation sequencing and confirmed by Sanger sequencing. A new clinical scoring system was developed to quantitatively assess the clinical severity of OI and the genotype-phenotype relationship was analyzed. The independent sample t-test, analysis of variance, Mann-Whitney U-test, Chi-squared test, Pearson correlation, and multiple linear regression were applied for statistical analyses. Results:. Among 161 patients with OI, 32.9% missense mutations, 16.8% non-sense mutations, 24.2% splice-site mutations, 24.8% frameshift mutations, and 1.2% whole-gene deletions were identified, of which 38 variations were novel. These mutations led to 53 patients carrying qualitative defects and 67 patients carrying quantitative defects in type I collagen. Compared to patients with quantitative mutations, patients with qualitative mutations had lower alkaline phosphatase level (296 [132, 346] U/L vs. 218 [136, 284] U/L, P = 0.009) and higher clinical score (12.2 ± 5.3 vs. 7.4 ± 2.4, P

Background Osteogenesis imperfecta (OI) is a phenotypically and genetically heterogeneous bone disease characterized by bone fragility and recurrent fractures. X‐linked inherited OI with mutation in PLS3 is so rare that its genotype–phenotype characteristics are not available. Methods We designed a novel targeted next‐generation sequencing (NGS) panel with the candidate genes of OI to detect pathogenic mutations and confirmed them by Sanger sequencing. The phenotypes of the patients were also investigated. Results The proband, a 12‐year‐old boy from a nonconsanguineous family, experienced multiple fractures of long bones and vertebrae and had low bone mineral density (BMD Z‐score of −3.2 to −2.0). His younger brother also had extremity fractures. A novel frameshift mutation (c.1106_1107insGAAA; p.Phe369Leufs*5) in exon 10 of PLS3 was identified in the two patients, which was inherited from their mother who had normal BMD. Blue sclerae were the only extraskeletal symptom in all affected individuals. Zoledronic acid was beneficial for increasing BMD and reshaping the compressed vertebral bodies of the proband. Conclusion We first identify a novel mutation in PLS3 that led to rare X‐linked OI and provide practical information for the diagnosis and treatment of this disease., A novel frameshift mutation was identified to cause X‐linked osteogenesis imperfecta (OI) in this study. Clinical hallmarks of the extremely rare disease were recurrent fractures. Bisphosphonates (BPs) were effective for these patients. Our findings may provide helpful information for clinical diagnosis and management of X‐linked OI.

We identified a novel large fragment deletion from intron 9 to 3’UTR in PLS3 (E10-E16del) in one Chinese boy with X-linked early-onset osteoporosis and vertebral fractures, which expanded the pathogenic spectrum of X-linked early-onset osteoporosis. Treatment with zoledronic acid was beneficial for increasing BMD and reshaping the vertebral bodies of this patient. X-linked early-onset osteoporosis is a rare disease, which is characterized by low bone mineral density (BMD), vertebral compression fractures (VCFs), and/or long bone fractures. We aimed to detect the phenotype and the underlying pathogenic mutation of X-linked early-onset osteoporosis in a boy from a nonconsanguineous Chinese family. We investigated the pathogenic mutation of the patient with X-linked early-onset osteoporosis by targeted next-generation sequencing and confirmed it by Sanger sequencing. We also observed the effects of zoledronic acid on fracture frequency and BMD of the patient. Low BMD and multiple VCFs were the main phenotypes of X-linked early-onset osteoporosis. We identified a total of 12,229 bp deletion in PLS3, involving intron 9 to the 3’UTR (E10-E16 del). This large fragment deletion might be mediated by Alu repeats and microhomology of 26 bp at each breakpoint junction. Zoledronic acid treatment could significantly increase the Z-score of BMD and reshape the compressed vertebral bodies. We identified a large fragment deletion mutation in PLS3 for the first time and elucidated the possible mechanism of the deletion, which led to X-linked early-onset osteoporosis and multiple vertebral fractures. Our findings would enrich the etiology spectrum of this rare disease.

Fibrous dysplasia (FD) is a rare disorder characterized by pain, deformity, and pathologic fractures. McCune-Albright syndrome (MAS) includes a combination of FD, hyperfunctional endocrinopathy, and/or café-au-lait pigmentation. Surgery is generally ineffective in treating FD. This study aimed to evaluate the efficacy and safety of bisphosphonates (BPs) and compare the efficacy of different BPs in FD patients.In this retrospective clinical study, laboratory and clinical findings of 22 polyostotic FD cases all associated with MAS were recorded before and after therapy with BPs.Within the first year of therapy with BPs, the level of alkaline phosphatase (ALP) decreased by 30.3% of baseline in the alendronate cases and by 22.7 ± 16.9% and 34.1 ± 26.3% in the pamidronate (PAM) (n = 10) and zoledronic acid (ZA) (n = 11) groups, respectively. There was no significant difference ( P = .256) between the PAM and ZA groups in the rate of change in ALP levels. Bone pain was alleviated in 64% of the cases. Number of affected bones was positively correlated with baseline serum ALP levels ( r = 0.533; P = .011), which was the only significant factor affecting efficacy of BPs. BP treatment was safe and caused no obvious impairment on children's linear growth.Our results suggest that BPs may suppress high bone turnover to partially control the activity of the disease and are well tolerated in most patients. ZA has similar effects as PAM in controlling disease activity.ALP = alkaline phosphatase; β-CTX = C-terminal telopeptide of type I collagen; BP = bisphosphonate; BTM = bone turnover marker; FD = fibrous dysplasia; MAS = McCune-Albright syndrome; ONJ = osteonecrosis of the jaw; PAM = pamidronate; PFD = polyostotic fibrous dysplasia; ULN = upper limit of normal; ZA = zoledronic acid.

Key points The inheritance of two defective alleles of SLC4A4, the gene that encodes the widely-expressed electrogenic sodium bicarbonate cotransporter NBCe1, results in the bicarbonate-wasting disease proximal renal tubular acidosis (pRTA). In the present study, we report the first case of compound-heterozygous inheritance of pRTA (p.Arg510His/p.Gln913Arg) in an individual with low blood pH, blindness and neurological signs that resemble transient ischaemic attacks. We employ fluorescence microscopy on non-polarized (human embryonic kidney) and polarized (Madin–Darby canine kidney) renal cell lines and electrophysiology on Xenopus oocytes to characterize the mutant transporters (R510H and Q913R). Both mutant transporters exhibit enhanced intracellular retention in renal cells, an observation that probably explains the HCO3− transport deficit in the individual. Both mutants retain a close-to-normal per molecule Na+/HCO3− cotransport activity in Xenopus oocytes, suggesting that they are suitable candidates for folding-correction therapy. However, Q913R expression is uniquely associated with a depolarizing, HCO3− independent, Cl−-conductance in oocytes that could have pathological consequences if expressed in the cells of patients. Abstract Proximal renal tubular acidosis (pRTA) is a rare, recessively-inherited disease characterized by abnormally acidic blood, blindness, as well as below average height and weight. pRTA is typically associated with homozygous mutation of the solute carrier 4 family gene SLC4A4. SLC4A4 encodes the electrogenic sodium bicarbonate cotransporter NBCe1, a membrane protein that acts to maintain intracellular and plasma pH. We present the first description of a case of compound-heterozygous inheritance of pRTA. The individual has inherited two mutations in NBCe1: p.Arg510His (R510H) and p.Gln913Arg (Q913R), one from each parent. In addition to the usual features of pRTA, the patient exhibits unusual signs, such as muscle spasms and fever. We have recreated these mutant transporters for expression in model systems. We find that both of the mutant proteins exhibit substantial intracellular retention when expressed in mammalian renal cell lines. When expressed in Xenopus oocytes, we find that the R510H and Q913R-mutant NBCe1 molecules exhibit apparently normal Na+/HCO3− cotransport activity but that Q913R is associated with an unusual HCO3− independent anion-leak. We conclude that a reduced accumulation of NBCe1 protein in the basolateral membrane of proximal-tubule epithelia is the most probable cause of pRTA in this case. We further note that the Q913R-associated anion-leak could itself be pathogenic if expressed in the plasma membrane of mammalian cells, compromising the benefit of strategies aiming to enhance mutant NBCe1 accumulation in the plasma membrane.

The carbonic anhydrase II (CAII) deficiency syndrome is a rare autosomal recessive osteopetrosis with renal tubular acidosis (RTA) and cerebral calcifications (MIM259730). CAII deficiency syndrome is caused by mutations in the gene CAII, which encodes the enzyme carbonic anhydrase II. CAII mutations are rarely reported in the Asian population. Here, we described two unrelated CAII deficiency families of Chinese Han origin with clinical and genetic analysis. Altogether, 106 subjects, including 2 probands, 4 unaffected family members from two non-consanguineous Chinese families, and 100 healthy controls were recruited. All seven exons and the exon-intron boundaries of the CAII gene were amplified and directly sequenced. Reverse transcription PCR (RT-PCR) was used to study the effect of splice site mutation. All clinical and biochemical parameters of the probands were collected. Two novel mutations of CAII gene were identified by mutational analysis: A nonsense mutation in exon 4 (c.T381C p.Y127X) in both families; a splice mutation at the splice donor site of intron 3 (c.350+2T>C, IVS3+2T>C) in one family. The splice-site mutation causes exon 3 skipping in patient's mRNA resulting in an in-frame deletion and a novel premature stop codon. These mutations were predicted to result in a loss of function of CAII. This is the first report of CAII deficiency syndrome in Chinese population. Our findings extent the spectrum of CAII mutations observed in patients with CAII deficiency syndrome.

Aim: To investigate the association between LRP5 gene polymorphisms and response to alendronate in Chinese osteoporotic women. Materials & methods: Six hundred and thirty nine Chinese postmenopausal women with osteopenia or osteoporosis were included and received alendronate treatment. The A1330V polymorphism of LRP5 was investigated. Bone mineral density (BMD) and bone turnover markers (ALP and β-isomerized carboxy-telopeptide of type I collagen [β-CTX]) were measured before and after treatment. The correlation of LRP5 polymorphisms with changes in BMD and bone turnover biomarkers were analyzed after treatment. Results: After 12 months of treatment, participants with CC and CT genotypes had a larger increase in lumbar spine BMD and a larger decrease in serum β-CTX and ALP levels than those with TT genotype (all p < 0.001). No significant genotype–treatment interaction was found in hip BMD. Conclusion: The A1330V polymorphism of LRP5 is possibly correlated with response to alendronate treatment in Chinese women with osteoporosis, and the TT genotype could possibly predict a weak response to alendronate. Original submitted 31 October 2013; Revision submitted 13 January 2014

Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by recurrent fragile fractures. Serpin peptidase inhibitor, clade F, member 1 (SERPINF1) is known to cause a distinct, extremely rare autosomal recessive form of type VI OI. Here we report, for the first time, the detection of SERPINF1 mutations in Chinese OI patients. We designed a novel targeted next-generation sequencing panel of OI-related genes to identify pathogenic mutations, which were confirmed with Sanger sequencing and by co-segregation analysis. We also investigated the phenotypes of OI patients by evaluating bone mineral density, radiological fractures, serum bone turnover markers, and pigment epithelium-derived factor (PEDF) concentration. Six patients with moderate-to-severe bone fragility, significantly low bone mineral density, and severe deformities of the extremities were recruited from five unrelated families for this study. Six pathogenic mutations in SERPINF1 gene were identified, five of which were novel: (1) a homozygous in-frame insertion in exon 3 (c.271_279dup, p.Ala91_Ser93dup); (2) compound heterozygous mutations in intron 3 (c.283 + 1G > T, splicing site) and exon 5 (c.498_499delCA, p.Arg167SerfsX35, frameshift); (3) a homozygous frameshift mutation in exon 8 (c.1202_1203delCA, p.Thr401ArgfsX); (4) compound heterozygous missense mutation (c.184G > A, p.Gly62Ser) and in-frame insertion (c.271_279dup, p.Ala91_Ser93dup) in exon 3; and (5) a heterozygous nonsense mutation in exon 4 (c.397C>T + ?, p.Gln133X + ?). Serum PEDF levels were barely detectable in almost all subjects. We identified five novel mutations in SERPINF1 and confirmed the diagnostic value of serum PEDF level for the first time in Chinese patients with the extremely rare OI type VI.

Osteoporosis is a disease of disequilibrium between bone formation and bone loss, and vitamin D is one of the key hormones in the regulation of bone metabolism, the major role of which is to provide the proper micro-environment for bone mineralization. Vitamin D deficiency which has been defined by most experts as circulating 25-hydroxyvitamin D levels of less than 20 ng/mL (50 nmol/L) is widespread all over the world. As shown by the results of recent studies, vitamin D deficiency could increase the risk of low bone mineral density or osteoporosis, muscle disorders, falls, and as a matter of course, fractures due to both osteoporosis and falls. Long-term supplementation of vitamin D and calcium are good prevention measures for osteoporosis, falls and fractures. At the same time, they are essential components of osteoporosis management. Many studies show that sufficient vitamin D intake could increase bone mass, and decrease the risk of falls and fractures.

A normal reference value of parathyroid hormone (PTH) was established for the first time in a large sample of healthy Chinese subjects by completely excluding interference of vitamin D deficiency. A high PTH level correlated significantly with an elevated bone turnover and a reduced bone mineral density (BMD). The aims of this study are to establish a normal reference value for serum PTH and to evaluate the effect of parathyroid gland status on bone turnover and BMD. Our cross-sectional study included 1436 healthy individuals from 5 different Chinese cities. Concentrations of serum PTH, 25-hydroxyvitamin D (25OHD), procollagen I N-terminal peptide (P1NP, a bone formation marker), and carboxyl-terminal telopeptide of type I collagen (β-CTX, a bone resorption marker) were measured by electrochemiluminescence immunoassay. BMD was measured by dual-energy X-ray absorptiometry. The relation of PTH concentration to age, gender, height, and weight was examined. Reference values of PTH were established for all subjects and for subjects categorized by serum 25OHD concentrations. Correlations of PTH levels with bone turnover biomarkers and BMD were statistically analyzed. Reference values of PTH were 8.84–69.95 pg/mL in all the subjects and 7.48–60.73 and 5.83–56.78 pg/mL in the subjects with serum 25OHD concentrations of ≥20 and ≥30 ng/mL, respectively. Serum PTH showed a negative linear correlation with 25OHD, and the breakpoint was 18.21 ng/mL, below which the PTH level rapidly increased. The increase in PTH levels with age showed a positive linear correlation with P1NP and β-CTX concentrations and a negative linear correlation with BMD at the lumbar spines and the femoral neck. A reference value of PTH was established in a large sample of healthy Chinese subjects according to 25OHD status, gender, and age. A high PTH level correlated significantly with an elevated bone turnover and a reduced BMD.

Osteopetrosis is a group of genetic bone disorders. Mutations in the chloride channel 7 gene (CLCN7) lead to chloride channel defect, which results in autosomal dominant osteopetrosis type II (ADO-II), autosomal recessive osteopetrosis (ARO), and intermediate autosomal recessive osteopetrosis (IARO). In the present study, we identified seven novel mutations of the CLCN7 gene and reported the first case of IARO with compound heterozygous mutation in Chinese population. Osteopetrosis is a heritable bone disorder due to the deficiency of or function defect in osteoclasts. Mutations in the CLCN7 lead to chloride channel defects, which result in osteopetrosis with diverse severity ranging from asymptomatic or relatively mild symptoms in ADO-II to the very severe phenotype in ARO. Heterozygous mutations in CLCN7 are associated to ADO-II, while homozygous and compound heterozygous mutations in CLCN7 may result in ARO and IARO. To date, a total of 24 mutations in CLCN7 were identified in ADO-II, and only 3 mutations were identified in IARO. In the present study, we reported seven unrelated ADO-II patients and one IARO patient from Chinese population and elucidated the characteristics of CLCN7 gene mutations in these patients. All 25 CLCN7 exons and exon-intron boundaries from genomic DNA were amplified and sequenced in eight affected individuals suffering from ADO-II/IARO. The clinical, biochemical, and radiographic analysis were evaluated to compare the differences between ADO-II and IARO both in genotype and phenotype. The results showed that there were seven novel CLCN7 mutations identified in these ADO-II/IARO patients, including six heterozygous missense mutations (p.L224R, p.S290Y, p.R326G, p.G347R, p.S473N, and p.L564P) and a novel splice mutation (p.K691FS). The compound heterozygous mutations (p.L224R and p.K691FS) were firstly observed in one IARO patient. The present study would enrich the database of CLCN7 mutations and improve our understanding of this heritable bone disorder.

Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acro-osteolysis, frequent fractures, and skull deformities. Mutation in the gene encoding cathepsin K (CTSK), which is a lysosomal cysteine protease, has been found to be responsible for this disease. Here we reported a consanguineous Chinese family with 1 affected individual demonstrating autosomal recessive pycnodysostosis with recurrent kidney stone, a new clinical manifestation which has not been reported in patients of pycnodysostosis before. To identify the pathogenic mutation, we evaluated the patient clinically, biochemically, and radiographically. To screen for mutations in the CTSK gene of the patient and his family members, all of its exons and exon-intron junctions were PCR amplified from genomic DNA and sequenced. Sequence analysis of the patient's CTSK gene revealed homozygosity for a missense mutation (c.746T>C) in exon 6, which leads to amino change (p.Ile249Thr) in the mature CTSK protein. This mutation was firstly reported by Michela Donnarumma and his colleagues in 2007 in a Spanish family. Our study strengthens the role of this particular mutation in the pathogenesis of pycnodysostosis.

The efficacy and safety of intravenous ibandronate were evaluated in postmenopausal osteoporosis women in China. In this multicenter, positive drug-controlled study, 158 postmenopausal osteoporotic women were randomized to receive 2 mg ibandronate given intravenously once every 3 months or 70 mg alendronate given orally once per week. All women also received supplemental calcium (500 mg) and vitamin D (200 IU) daily. One hundred fifty-one patients completed the 1-year study. Ibandronate produced mean increases in bone mineral density (BMD) by 4.27% at the lumbar spine, 3.48% at the femoral neck, and 2.03% at the trochanter. Mean increases in BMD by 4.24% at the lumbar spine, 2.72% at the femoral neck, and 2.99% at the trochanter were observed in the alendronate group. No significant difference was found between the two groups in BMD in all sites measured. Significant decreases in serum c-telopeptide of type I collagen (CTX) and alkaline phosphatase (ALP) were found in the two groups after 1 and 3 months of treatment, respectively; these serum CTX and ALP levels were then maintained at the decreased levels throughout the study period (12 months). No changes of stature were found in the patients of the two groups. Adverse events were similar in the two groups, except more mild muscle pain was observed in the first month after infusion of ibandronate than with oral alendronate (P < 0.001). The results observed in Chinese patients may support the observation that intravenous ibandronate significantly reduced bone resorption and increased BMD with good tolerance in Chinese postmenopausal osteoporotic women. Use of intravenous ibandronate possibly could potentially improve compliance as compared with other oral bisphosphonates because it may avoid the peptic side effects of oral bisphosphonate.