Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation

Osteosclerotic metaphyseal dysplasia (OSMD) is a rare autosomal recessive sclerosing skeletal dysplasia. We report on a 34-year-old patient with sandwich vertebrae, platyspondyly, osteosclerosis of the tubular bones, pathologic fractures, and anemia. In the third decade, he developed osteonecrosis of the jaws, which was progressive in spite of repeated surgical treatment over a period of 11 years. An iliac crest bone biopsy revealed the presence of hypermineralized cartilage remnants, large multinucleated osteoclasts with abnormal morphology, and inadequate bone resorption typical for osteoclast-rich osteopetrosis. After exclusion of mutations in TCIRG1 and CLCN7 we performed trio-based exome sequencing. The novel homozygous splice-site mutation c.261G>A in the gene LRRK1 was found and co-segregated with the phenotype in the family. cDNA sequencing showed nearly complete skipping of exon 3 leading to a frameshift (p.Ala34Profs*33). Osteoclasts differentiated from the patient's peripheral blood monocytes were extremely large. Instead of resorption pits these cells were only capable of superficial erosion. Phosphorylation of L-plastin at position Ser5 was strongly reduced in patient-derived osteoclasts showing a loss of function of the mutated LRRK1 kinase protein. Our analysis indicates a strong overlap of LRRK1-related OSMD with other forms of intermediate osteopetrosis, but an exceptional abnormality of osteoclast resorption. Like in other osteoclast pathologies an increased risk for progressive osteonecrosis of the jaws should be considered in OSMD, an intermediate form of osteopetrosis

Serial two-photon tomography for automated ex vivo mouse brain imaging

Here we describe an automated method, named serial two-photon (STP) tomography, that achieves high-throughput fluorescence imaging of mouse brains by integrating two-photon microscopy and tissue sectioning. STP tomography generates high-resolution datasets that are free of distortions and can be readily warped in three dimensions, for example, for comparing multiple anatomical tracings. This method opens the door to routine systematic studies of neuroanatomy in mouse models of human brain disorders

Rector Academiae Lipsiensis Cives Omnes ac Singulos, ut Funus ... Dn. Sebastiani Oheimii Lipsiensis, L. L. & Politiorum Artium Cultoris perstrenui, hora I. frequentissimo comitatu prosequantur, ea, qua par, humanitate rogat & obtestatur : [P. P. Lipsiae V. Kal. Novemb. A.E.C. M. DC.LXXIII.]

RECTOR ACADEMIAE LIPSIENSIS CIVES OMNES AC SINGULOS, UT FUNUS ... DN. SEBASTIANI OHEIMII LIPSIENSIS, L. L. & POLITIORUM ARTIUM CULTORIS PERSTRENUI, HORA I. FREQUENTISSIMO COMITATU PROSEQUANTUR, EA, QUA PAR, HUMANITATE ROGAT & OBTESTATUR : [P. P. LIPSIAE V. KAL. NOVEMB. A.E.C. M. DC.LXXIII.] Rector Academiae Lipsiensis Cives Omnes ac Singulos, ut Funus ... Dn. Sebastiani Oheimii Lipsiensis, L. L. & Politiorum Artium Cultoris perstrenui, hora I. frequentissimo comitatu prosequantur, ea, qua par, humanitate rogat & obtestatur : [P. P. Lipsiae V. Kal. Novemb. A.E.C. M. DC.LXXIII.] (1) Titelblatt (1) Text (3

Dynamics of Skeletal Status under Optimized Management during Subsequent Pregnancy in Three Women with a History of Pregnancy‐ and Lactation‐Associated Osteoporosis Carrying pathogenic Variants in WNT1 and LRP5

Abstract Pregnancy‐ and lactation‐associated osteoporosis (PLO) is a rare but clinically highly relevant condition, characterized by reduced bone mineral density (BMD) and acute onset of severe pain due to symptomatic bone marrow edema of the hip or vertebral and/or insufficiency fractures, among others. Previous reports showed a high frequency of hereditary bone disorders unmasked by PLO, predisposing for more severe forms. To date, no data on the risk for additional fractures during subsequent pregnancy in women with PLO and genetic bone disorder have been available. To address this question, we retrospectively analyzed the clinical, biochemical, and densitometric course of three women with a history of PLO and detected variants in WNT1 or LRP5 and subsequent pregnancies. Calcium homeostasis and bone turnover were optimized by basic treatment, and timely initiation of weaning was recommended. Teriparatide treatment for 12 months under strict contraception was initiated in one woman after the diagnosis of PLO. In none of the women did additional fractures or symptomatic bone marrow edemas occur, and BMD by dual‐energy X‐ray absorptiometry as bone microarchitecture by high‐resolution peripheral quantitative computed tomography remained stable. In conclusion, this report expands the understanding of this rare but severe condition and helps to improve clinical counseling and management. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

Topographia Metrica Misniae Compendiosae, Lipsiae, emporii qua magnificentissimi qua opulentissimi Viris Magnificis, Nobilissimis, Excellentissimis Iuxta Et Consultissimis Dn. Christophoro Pinckero, ... Dn. Friderico Kuhlewein ... Tum Etiam Magnificentia ... Dn. Johanni Philippi ... Dn. Paulo Wagnero ... Dn. Philippo Jacobo Lindnero ... et ... Dn. Quirino Schachero ... Dn. Jacobo Meuero ... Dn. Sebastiano Oheim ... Dn. Marco Scipioni ... Dn. Wolffgango Peilickio ... Dn. Johanni Seidelio ... Dn. Sigismundo Finckelthusio ... Dn. Heinrico Gramano ... dedicata a Jeremia Wittichio ...

TOPOGRAPHIA METRICA MISNIAE COMPENDIOSAE, LIPSIAE, EMPORII QUA MAGNIFICENTISSIMI QUA OPULENTISSIMI VIRIS MAGNIFICIS, NOBILISSIMIS, EXCELLENTISSIMIS IUXTA ET CONSULTISSIMIS DN. CHRISTOPHORO PINCKERO, ... DN. FRIDERICO KUHLEWEIN ... TUM ETIAM MAGNIFICENTIA ... DN. JOHANNI PHILIPPI ... DN. PAULO WAGNERO ... DN. PHILIPPO JACOBO LINDNERO ... ET ... DN. QUIRINO SCHACHERO ... DN. JACOBO MEUERO ... DN. SEBASTIANO OHEIM ... DN. MARCO SCIPIONI ... DN. WOLFFGANGO PEILICKIO ... DN. JOHANNI SEIDELIO ... DN. SIGISMUNDO FINCKELTHUSIO ... DN. HEINRICO GRAMANO ... DEDICATA A JEREMIA WITTICHIO ... Topographia Metrica Misniae Compendiosae, Lipsiae, emporii qua magnificentissimi qua opulentissimi Viris Magnificis, Nobilissimis, Excellentissimis Iuxta Et Consultissimis Dn. Christophoro Pinckero, ... Dn. Friderico Kuhlewein ... Tum Etiam Magnificentia ... Dn. Johanni Philippi ... Dn. Paulo Wagnero ... Dn. Philippo Jacobo Lindnero ... et ... Dn. Quirino Schachero ... Dn. Jacobo Meuero ... Dn. Sebastiano Oheim ... Dn. Marco Scipioni ... Dn. Wolffgango Peilickio ... Dn. Johanni Seidelio ... Dn. Sigismundo Finckelthusio ... Dn. Heinrico Gramano ... dedicata a Jeremia Wittichio ... ([1]) Titelseite ([1]) Text ([2]