High Prevalence of Osteoporosis and Morphometric Vertebral Fractures in Indian Males Aged 60 Years and Above: Should Age for Screening Be Lowered?

Current guidelines recommend bone mineral density (BMD) measurement in asymptomatic men above age 70 years and vertebral fracture (VF) assessment above 80 years with T-score <-1.0 with risk factors. We studied the prevalence of osteoporosis and morphometric VF in asymptomatic males aged 60 years and above in North India. Free-living community-dwelling men (n = 241, age: mean ± standard deviation 68.0 ± 6.2 years) underwent a detailed history, physical examination, biochemical evaluation, and BMD measurements at 3 sites: lumbar spine, total hip (TH), and femoral neck (FN). Morphometric VF were assessed by instant vertebral assessment using Genant et al's semiquantitative method. We observed osteoporosis, osteopenia, and normal BMD in 19%, 56%, and 25% of subjects, respectively. The decade wise prevalence of osteoporosis in the age groups 60-70 years, 71-80 years, and >80 years was 16.9%, 17%, and 50%, respectively. Mean serum 25OHD levels were 17.2 ± 10.3 ng/mL. Vitamin D deficiency (<20 ng/mL) and secondary hyperparathyroidism (plasma intact parathyroid hormone >65 ng/mL) were present in 68.8% and 45.4%, respectively. VF were present in 29.6% subjects (grade I: 58%, grade II: 32.4%, and grade III: 8.8%). Age and iPTH had significant negative correlation with BMD at FN and TH. Serum 25OHD had no correlation with BMD at any site. The prevalence of VF was positively associated with age (p = 0.018) and negatively associated with BMD at FN (p = 0.002) and TH (p = 0.013). Osteoporosis and VF are common in asymptomatic Indian males aged 60 years and above. Screening for osteoporosis and instant vertebral assessment may be recommended earlier than currently existing guidelines.

Utility of Osteoporosis Self-Assessment Tool as a Screening Tool for Predicting Osteoporosis in Indian Men.

The osteoporosis self-assessment tool (OSTA) predicts the risk of osteoporosis in an individual. It is a simple calculation-based tool [wt (kg) - age (yr)/5] and can be used for measuring bone mineral density (BMD). However, OSTA is influenced by ethnicity. We studied the performance of OSTA index as a screening tool for osteoporosis in 257 community-dwelling North Indian men above 50 yr age. Each subject underwent a detailed clinical, dietary, anthropometric, and biochemical assessment and bone density measurement using dual-energy X-ray absorptiometry. As per World Health Organization criteria, osteoporosis, osteopenia, and normal BMD were observed in 17.9%, 58.8%, and 23.3%, respectively. OSTA index ranged between -6.4 and 8.8. OST index ≤2 predicted osteoporosis with a sensitivity of 95.7% and a specificity of 33.6% and an area under the curve for a receiver operating characteristic curve of 0.702. The OSTA index is an effective screening tool for measuring BMD in elderly Indian men and can be used by primary care physicians.

Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats.

The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks) bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH)2 vitamin D3 (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective.

Crystal structure of (5R)-5-[(1S)-1,2-di-hydroxy-eth-yl]-4-meth-oxy-3-phenyl-2,5-di-hydro-furan-2-one.

In the title compound, C13H14O5, the furan ring is essentially planar [maximum deviation = 0.031 (3) Å] with a stereogenic center (R) at the sp (3) hybridized C atom. The C atom bearing the dihy-droxy ethyl group is S. The absolute configuration is based on the precursor in the synthesis. The two O-H groups are in an anti conformation with respect to each other. The mean plane of the furan-one group is twisted by 8.2 (4)° from that of the phenyl ring. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds involving furan-one C=O groups and symmetry-related hy-droxy groups, forming a two-dimensional network parallel to (001). Weak C-H⋯O hydrogen bonds are observed within the two-dimensional network.

Tri-phenyl-tellurium chloride.

The asymmetric unit of the title compound, C18H15ClTe, contains two mol-ecules which are in inverted orientations. The compound displays a tetra-hedral geometry around the Te atom in spite of there being five electron domains. This is attributed to the fact that the lone pair is not sterically active. The dihedral angles between the three phenyl rings are 76.51 (16)/73.75 (16)/71.06 (17) and 78.60 (17)/77.67 (16)/79.11 (16)° in the two mol-ecules. The crystal packing features eight C-H⋯π inter-actions.

Intra-operative parathyroid hormone kinetics and influencing factors with high baseline PTH: a prospective study.

BACKGROUND AND OBJECTIVE: Intra-operative parathyroid hormone (IOPTH) kinetics and therefore the efficacy of IOPTH utilization as a predictor of cure are likely to be affected by baseline IOPTH levels, vitamin D deficiency and parathyroid weight. PATIENTS AND METHODS: Consecutive subjects with primary hyperparathyroidism (PHPT, n = 51) undergoing parathyroidectomy with IOPTH monitoring were studied prospectively during the period October 2009-November 2011. Samples were collected pre-incision, pre-excision and post-excision (5, 10, 15 min). Iterative analysis of IOPTH kinetics and half-life calculation was carried out in subgroups. Nonparametric testing was used for group statistics. RESULTS: Hypovitaminosis D (25(OH)D3 < 50 nm) was present in 39 (76%), serum PTH > 1000 ng/l in 23 (45%), and giant parathyroid adenoma (weight > 3000 mg) in 23 (45%). The percentage drop at 10 min was significantly higher in large adenomas (weight > 3000 mg). Miami and 5 min criteria showed the highest negative predictive value and maximum accuracy. The average percentage IOPTH drop observed at 5 min post-excision was 79.8%. Kinetic analysis showed a mean half-life of PTH of 2.57 ± 0.27 min (range: 0.07-11.55). CONCLUSION: IOPTH monitoring is reliable even in patients with extremely high baseline IOPTH value, with a greater percentage drop at 5 and 10 min post-excision. In patients with high baseline IOPTH, a 50% decay in PTH value at 5 min may be indicative of cure, obviating the need for 10 and 15 min samples. IOPTH kinetics are altered by adenoma weight but not affected by vitamin D status or baseline IOPTH levels.

[meso-5,10,15,20-Tetra-kis(3-methyl-thio-phen-2-yl)porphyrinato-κ(4) N,N',N'',N''']nickel(II) benzene hemisolvate.

In the title compound, [Ni(C40H28N4S4)]·0.5C6H6, the Ni(II) atom is in a square-planar geometry defined by four pyrrole N atoms. There is considerable buckling in the porphyrin ring with the dihedral angles between the N4 donor set and the pyrrole rings being in the range 16.24 (5)-22.47 (5)°. Each of the six-membered chelate rings is twisted about an Ni-N bond and the dihedral angles between diagonally opposite chelate rings are 21.36 (4) and 23.87 (4)°; each pair of rings is oriented in opposite directions. The methyl-thienyl rings are twisted out of the plane of the central N4 core with dihedral angles in the range 75.98 (2)-88.70 (5)°. All four methyl-thienyl groups are disordered over two sets of sites, as is commonly found with such groups, with occupancies of 0.553 (8):0.447 (8), 0.579 (7):0.421 (7), 0.796 (6):0.204 (6) and 0.956 (7):0.044 (7). The benzene solvent mol-ecule was found to be present in half-occupancy.

1-(2-Furo-yl)-3-(2-meth-oxy-4-nitro-phen-yl)thio-urea.

The asymmetric unit of the title compound, C13H11N3O5S, contains two independent mol-ecules, which are linked by a pair of inter-molecular N-H⋯S hydrogen bonds, forming an R2(2)(8) ring motif. The central thio-urea core forms dihedral angles of 3.02 (12) and 14.00 (10)° with the essentially planar furoyl groups [maximum deviations = 0.030 (2) and 0.057 (2) Å] in the two mol-ecules and dihedral angles of 2.43 (13) and 8.03 (12)° with the benzene rings. The dihedral angles between the furoyl and benzene rings in the two mol-ecules are 3.97 (10) and 5.98 (9)°. The trans-cis geometry of the thio-urea group is stabilized by three intra-molecular N-H⋯O hydrogen bonds involving carbonyl and meth-oxy O atoms with the H atom of the cis-thio-amide group and between furan O atom and the other thio-amide H atom. There is also a weak intra-molecular C-H⋯S inter-action in each mol-ecule.

(E)-2-[(Furan-2-yl)methyl-idene]-7-methyl-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

In the title mol-ecule, C(18)H(15)NO(2), the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1317 (12) Å]. The pyrrole ring makes dihedral angles of 1.01 (8) and 18.56 (10)° with the benzene and furan rings, respectively. The cyclo-hexene ring adopts a half-chair conformation. In the crystal, pairs of N-H⋯O hydrogen bonds form an R(2) (2)(10) ring. Mol-ecules are further linked by C-H⋯O and C-H⋯π inter-actions, forming a three-dimensional network.

7-Methyl-1-phenyl-1,10-di-hydro-pyrazolo-[3,4-a]carbazole.

In the title mol-ecule, C20H15N3, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1082 (15) Å]. The pyrrole ring makes dihedral angles of 3.17 (8)/4.10 (9), 7.20 (9) and 44.62 (9)° with the fused benzene, pyrazole and phenyl rings, respectively. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming an infinite chain along [010]. Mol-ecules are further linked by nine π-π [centroid-centroid distances vary from 3.6864 (11) to 3.9802 (11) Å] and one C-H⋯π inter-action, forming a three-dimensional network.

Synthesis, crystal structure, Hirshfeld surface analysis, DFT and NBO study of ethyl 1-(4-fluoro-phen-yl)-4-[(4-fluoro-phen-yl)amino]-2,6-diphenyl-1,2,5,6-tetra-hydro-pyridine-3-carboxyl-ate.

The title com-pound, C32H28F2N2O2, a highly functionalized tetra-hydro-pyridine, was synthesized by a one-pot multi-com-ponent reaction of 4-fluoro-aniline, ethyl aceto-acetate and benzaldehyde at room temperature using sodium lauryl sulfate as a catalyst. The com-pound crystallizes with two mol-ecules in the asymmetric unit. The tetra-hydro-pyridine ring adopts a distorted boat conformation in both mol-ecules and the dihedral angles between the planes of the fluoro-substituted rings are 77.1 (6) and 77.3 (6)°. The amino group and carbonyl O atom are involved in an intra-molecular N-H⋯O hydrogen bond, thereby generating an S(6) ring motif. In the crystal, mol-ecules are linked by C-H⋯F hydrogen bonds forming a three-dimensional network and C-H⋯π inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H⋯H (47.9%), C⋯H/H⋯C (30.7%) and F⋯H/H⋯F (12.4%) contacts. The optimized structure calculated using density functional theory (DFT) at the B3LYP/6-311+G(2d,p) level is compared with the experimentally determined molecular structure in the solid state. The HOMO-LUMO behaviour was used to determine the energy gap and the Natural Bond Orbital (NBO) analysis was done to study donor-acceptor interconnections.

Role of B12 and homocysteine status in determining BMD and bone turnover in young Indians.

Vitamin B(12) (B(12)) deficiency and hyperhomocysteinemia (HHcy) are independent risk factors for low bone mineral density (BMD) and fracture risk. We studied the role of HHcy and B(12) deficiency in determining the peak bone mass in Indians. Randomly selected 151 healthy young adult subjects (females 100, mean age: 26 yr) underwent evaluation of dietary intake of calcium and B(12); sun exposure; estimation of BMD by dual-energy X-ray absorptiometry at total hip, forearm, and lumbar spine; serum 25(OH)D(3); intact parathyroid hormone; B(12); homocysteine (Hcy); and bone turnover markers (BTMs) serum crosslaps, N-mid osteocalcin, and bone-specific alkaline phosphatase. Hypovitaminosis D (serum 25OHD(3)<20 ng/mL) and serum ALP level >150 IU/L were seen in 83% and 27%, respectively. Median serum B(12) and Hcy levels were 140 pg/mL (interquartile range [IQR]: 72-230 pg/mL) and 18 µmol/L (IQR 14-32 µmol/L); B(12) deficiency (serum B(12)<200 pg/mL) and HHcy (serum Hcy>30 µmol/L) were present in 71% and 68%, respectively. Low BMD (Z-score <-2.0) was present in 17% of subjects. There was no significant correlation between serum Hcy, folate, B(12), BTM, and BMD. BMD was predicted by height, weight, and body mass index. Young Indian healthy adults have high prevalence of hypovitaminosis D, B(12) deficiency, and HHcy. There is no correlation of serum B(12), folate, and Hcy status with BTMs and BMD in young, healthy, vegetarian Indian adults. Anthropometric variables predict BMD in young Indians.

3-[(Furan-2-yl)carbon-yl]-1-(pyrimi-din-2-yl)thio-urea.

The title compound, C10H8N4O2S, was synthesized from furoyl isothio-cynate and 2-amino-pyrimidine in dry acetone. The two N-H groups are in an anti conformation with respect to each other and one N-H group is anti to the C=S group while the other is syn. The amide C=S and the C=O groups are syn to each other. The mean plane of the central thio-urea fragment forms dihedral angles of 13.50 (14) and 5.03 (11)° with the furan and pyrimidine rings, respectively. The dihedral angle between the furan and pyrimidine rings is 18.43 (10)°. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯N hydrogen bond generating an S(6) ring motif. In the crystal, mol-ecules are linked by pairs of N-H⋯N and weak C-H⋯S hydrogen bonds to form inversion dimers.

1-(Naphthalen-1-yl)-3-[(thio-phen-2-yl)carbon-yl]thio-urea.

In the title compound, C(16)H(12)N(2)OS(2), the dihedral angles between the mean planes of the central thio-urea core and the thio-phene ring and the naphthalene ring system are 1.8 (2) and 6.45 (18)°, respectively. The mol-ecule adopts a trans-cis conformation with respect to the position of thio-phenoyl and naphthyl groups relative to the S atom across the thiourea C-N bonds. Both the thio-phene ring and the sulfanyl-idene S atom are disordered over two sets of sites with occupancies of 0.862 (3):0.138 (3) and 0.977 (3):0.023 (3), respectively. An intra-molecular N-H⋯O hydrogen bond is observed. The crystal packing features two N-H⋯S hydrogen bonds.

4-Isopropyl-5,5-dimethyl-2-sulfanyl-1,3,2-dioxaphosphinane 2-sulfide.

The title compound, C(8)H(17)O(2)PS(2), displays a distorted tetra-hedral geometry around the P atom. The P atom is part of a six-membered ring with an isopropyl group in the equatorial position. The mol-ecules are linked by S-H⋯S hydrogen bonds in the crystal packing.

Methyl 2-(thio-phene-2-carboxamido)-benzoate.

The title compound, C(13)H(11)NO(3)S, was synthesized from methyl anthranilate, triethyl-amine and 2-thio-phenoyl chloride in benzene. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond. The dihedral angle between the rings is 2.74 (12)°. In the crystal, C-H⋯O inter-actions link neighbouring mol-ecules into a three-dimensional network.

2-Chloro-7,8,9,10-tetra-hydro-cyclo-hepta-[b]indol-6(5H)-one.

In the title mol-ecule, C(13)H(12)ClNO, the dihedral angle between the benzene and pyrrole rings is 1.38 (9)°. The cyclo-heptene ring adopts a distorted twist chair and sofa conformation. Inter-molecular N-H⋯O hydrogen bonds form an R(2) (2)(10) loop in the crystal packing. Further, weak C-H⋯O and C-H⋯π (involving the benzene ring) inter-actions are found in the crystal structure.

Crystal structure, Hirshfeld surface analysis and DFT study of 2,2''-({[(1E,1'E)-(diselanedi-yl)bis-(2,1-phenyl-ene)]bis-(methane-ylyl-idene)}bis-(aza-neylyl-idene))bis-[3',6'-bis-(di-ethyl-amino)-4a',9a'-di-hydro-spiro-[isoindoline-1,9'-xanthen]-3-one].

The title compound, C70H70N8O4Se2, is a spiro bicyclic diselenide, made up of two [SeC6H4CH=N-N(CO)C6H4(C)C6H3NEt2(O)C6H3NEt2] units related by a twofold crystallographic symmetry element bis-ecting the diselenide bond. The compound crystallizes in a non-centrosymmetric polar space group (tetra-gonal, P b2) and the structure was refined as an inversion twin. The two diethyl amine groups and their attached phenyl groups of the xanthene ring are disordered over two orientations, with occupancies of 0.664 (19)/0.336 (19) and 0.665 (11)/0.335 (11), respectively. The dihedral angles between the mean planes of the central isoindoline and the phenyl rings are 26.8 (2) and 2.5 (4)°, respectively. The mean plane of the central xanthene ring forms dihedral angles of 2.0 (5), 8.8 (5), 1.7 (5) and 7.9 (6)° with the peripheral phenyl rings. The isoindoline and xanthene rings subtend a dihedral angle of 89.8 (2)°. The mol-ecular conformation is stabilized by an intra-molecular C-H⋯O hydrogen bond generating an S(6) ring motif. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds together with C-H⋯π (ring) inter-actions, forming a three-dimensional network. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H⋯H (68.1%), C⋯H/H⋯C (21.2%) and O⋯H/H⋯O (8.7%) contacts. The optimized structure calculated using density functional theory (DFT) at the B3LYP/6 - 31 G(d) level is compared with the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behaviour was used to determine the energy gap and the mol-ecular electrostatic potential (MEP) of the compound was investigated.

10,21-Dimethyl-2,7,13,18-tetraphenyl-3,6,14,17-tetraazatricyclo[17.3.1.1]tetracosa-1(23),2,6,8(24),9,11,13,17,19,21-decaene-23,24-diol cyclohexane 0.33-solvate.

The title compound, C(46)H(40)N(4)O(2)·0.33C(6)H(12), was obtained unintentionally as a product of an attempted synthesis of a cadmium(II) complex of the [2,6-{PhSe(CH(2))(2)N=CPh}(2)C(6)H(2)(4-Me)(OH)] ligand. The full tetra-imino-diphenol macrocyclic ligand is generated by the application of an inversion centre. The macrocyclic ligand features strong intra-molecular O-H⋯N hydrogen bonds. The dihedral angles formed between the phenyl ring incorporated within the macrocycle and the peripheral phenyl rings are 82.99 (8) and 88.20 (8)°. The cyclo-hexane solvent mol-ecule lies about a site of [Formula: see text] symmetry. Other solvent within the lattice was disordered and was treated with the SQUEEZE routine [Spek (2009). Acta Cryst. D65, 148-155].