2019
Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression
Lotinun S, Ishihara Y, Nagano K, Kiviranta R, Carpentier VT, Neff L, Parkman V, Ide N, Hu D, Dann P, Brooks D, Bouxsein ML, Wysolmerski J, Gori F, Baron R. Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression. Journal Of Clinical Investigation 2019, 129: 3058-3071. PMID: 31112135, PMCID: PMC6668688, DOI: 10.1172/jci122936.Peer-Reviewed Original ResearchConceptsLactation-induced bone lossParathyroid hormoneBone lossBone resorptionCathepsin KMilk calcium levelsParathyroid hormone suppressionSerum parathyroid hormoneRegulation of PTHOsteoclastic bone resorptionTrabecular bone volumeOsteocyte lacunar areaHormone suppressionHigh calcium demandOsteoclast numberCortical thicknessEffect of lactationCalcium levelsNormal rangeBone volumeCalcium demandExact mechanismLacunar areaResorptionSufficient calcium
2013
Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual
Mamillapalli R, VanHouten J, Dann P, Bikle D, Chang W, Brown E, Wysolmerski J. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual. Endocrinology 2013, 154: 3031-3042. PMID: 23782944, PMCID: PMC3749485, DOI: 10.1210/en.2012-2195.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBiological TransportBone DevelopmentBone ResorptionCalciumCrosses, GeneticFemaleGene Expression RegulationLactationLactoglobulinsMammary Glands, AnimalMiceMice, KnockoutMice, TransgenicMilkParathyroid HormoneParathyroid Hormone-Related ProteinReceptors, Calcium-SensingRNA, MessengerConceptsRenal calcium excretionCalcium excretionCalcium metabolismBone resorptionCalcium transportMilk calciumMammary glandAccelerated bone resorptionMammary-specific ablationMaternal calcium metabolismDietary calcium intakeCalcium sensing receptorCalcium-sensing receptorSecretion of PTHrPSkeletal calcium storesMilk PTHrPCalcium intakePTH secretionPTHrP secretionMaternal boneBone turnoverBone metabolismOnset of lactationMaternal circulationSystemic calciumOsteocytes remove and replace perilacunar mineral during reproductive cycles
Wysolmerski JJ. Osteocytes remove and replace perilacunar mineral during reproductive cycles. Bone 2013, 54: 230-236. PMID: 23352996, PMCID: PMC3624069, DOI: 10.1016/j.bone.2013.01.025.BooksConceptsBone lossLevels of PTHrPNegative calcium balanceLevels of estrogenPrincipal bone-resorbing cellsSkeletal calcium storesBone-resorbing cellsPTHrP levelsBone turnoverBone resorptionBone massMineral metabolismCalcium balanceRole of osteocytesCalcium storesMineral homeostasisOsteocytic osteolysisReproductive cycleOsteocytesSystemic demandsPericanalicular matrixCalciumLactationBone
2010
Increased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton
Ardeshirpour L, Brian S, Dann P, VanHouten J, Wysolmerski J. Increased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton. Endocrinology 2010, 151: 5591-5601. PMID: 21047946, PMCID: PMC2999486, DOI: 10.1210/en.2010-0566.Peer-Reviewed Original ResearchConceptsBone mineral densityBone lossEstrogen deficiencyMineral densityInfusion of PTHrPReversible bone lossLevels of estrogenCombination of OVXLeuprolide treatmentCentral hypogonadismGnRH agonistMaternal skeletonBone turnoverOsmotic minipumpsOsteoclast numberBone metabolismBone resorptionSurgical ovariectomyNulliparous micePTHrPOVXInfusionEstrogenLeuprolideModest declineIncreased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton
Ardeshirpour L, Brian S, Dann P, VanHouten J, Wysolmerski J. Increased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton. Endocrine Reviews 2010, 31: 940-940. DOI: 10.1210/edrv.31.6.9976.Peer-Reviewed Original ResearchBone mineral densityBone lossEstrogen deficiencyMineral densityInfusion of PTHrPReversible bone lossLevels of estrogenCombination of OVXLeuprolide treatmentCentral hypogonadismGnRH agonistMaternal skeletonBone turnoverOsmotic minipumpsOsteoclast numberBone metabolismBone resorptionSurgical ovariectomyNulliparous micePTHrPOVXInfusionEstrogenLeuprolideModest decline
2007
Conversations between breast and bone: Physiological bone loss during lactation as evolutionary template for osteolysis in breast cancer and pathological bone loss after menopause
Wysolmerski J. Conversations between breast and bone: Physiological bone loss during lactation as evolutionary template for osteolysis in breast cancer and pathological bone loss after menopause. BoneKEy Reports 2007, 4: 209-225. DOI: 10.1138/20070268.Peer-Reviewed Original ResearchBone lossBone resorptionBreast cancerParathyroid hormone-related proteinLow estrogen levelsPathological bone resorptionPost-menopausal womenPathological bone lossCalcium-sensing receptorPhysiological bone lossHormone-related proteinSkeletal calcium storesHypothalamic hypogonadismPTHrP levelsEstrogen levelsPTHrP productionSkeletal demineralizationMineral metabolismSkeletal responseBone diseaseNew therapiesCalcium storesBone recoveryBreastCalcium transportWeaning Triggers a Decrease in Receptor Activator of Nuclear Factor-κB Ligand Expression, Widespread Osteoclast Apoptosis, and Rapid Recovery of Bone Mass after Lactation in Mice
Ardeshirpour L, Dann P, Adams DJ, Nelson T, VanHouten J, Horowitz MC, Wysolmerski JJ. Weaning Triggers a Decrease in Receptor Activator of Nuclear Factor-κB Ligand Expression, Widespread Osteoclast Apoptosis, and Rapid Recovery of Bone Mass after Lactation in Mice. Endocrinology 2007, 148: 3875-3886. PMID: 17495007, DOI: 10.1210/en.2006-1467.Peer-Reviewed Original ResearchConceptsBone lossBone massBone turnoverReceptor activatorOsteoclast apoptosisRapid bone lossC-telopeptide levelsNumber of osteoclastsBone formation rateNuclear factor-kappaB ligand (RANKL) mRNANuclear factor-kappaB ligand (RANKL) expressionRapid recoveryLevels of osteocalcinCessation of lactationSkeletal anabolismPTH levelsCalcium metabolismBone resorptionBone histomorphometryBone microarchitectureCalcium levelsOsteoblast numberLigand expressionReciprocal decreaseBone recovery
2005
Continuous PTH and PTHrP Infusion Causes Suppression of Bone Formation and Discordant Effects on 1,25(OH)2Vitamin D
Horwitz MJ, Tedesco MB, Sereika SM, Syed MA, Garcia‐Ocaña A, Bisello A, Hollis BW, Rosen CJ, Wysolmerski JJ, Dann P, Gundberg C, Stewart AF. Continuous PTH and PTHrP Infusion Causes Suppression of Bone Formation and Discordant Effects on 1,25(OH)2Vitamin D. Journal Of Bone And Mineral Research 2005, 20: 1792-1803. PMID: 16160737, DOI: 10.1359/jbmr.050602.Peer-Reviewed Original ResearchConceptsContinuous infusionVitamin DBone formationPhosphorus handlingRenal calciumIGF-1Anabolic skeletal responseDoses of PTHVitamin D homeostasisVitamin D metabolismPlasma IGF-1Vitamin D productionVitamin D synthesisOsteoblastic bone formationHealthy young adultsRenal PTH receptorsContinuous PTHCalcemic responseD homeostasisPrimary hyperparathyroidismHumoral hypercalcemiaSerum calciumD metabolismBone turnoverBone resorptionHypercalcemia in Breast Cancer: An Echo of Bone Mobilization During Lactation?
DeMauro S, Wysolmerski J. Hypercalcemia in Breast Cancer: An Echo of Bone Mobilization During Lactation? Journal Of Mammary Gland Biology And Neoplasia 2005, 10: 157-167. PMID: 16025222, DOI: 10.1007/s10911-005-5398-9.BooksConceptsBreast cancer patientsBone resorptionCancer patientsBreast cancerParathyroid hormone-related proteinPathophysiology of hypercalcemiaMultiple skeletal metastasesPathological bone resorptionHormone-related proteinActivation of osteoclastsSecretion of cytokinesClass of drugsSkeletal calcium storesNormal breast cellsFrequent complicationSkeletal metastasesSignificant morbidityCalcium metabolismCurrent therapiesHypercalcemiaNew therapiesCalcium levelsOsteoclast differentiationCalcium storesPatients
2003
Mammary-specific deletion of parathyroid hormone–related protein preserves bone mass during lactation
VanHouten JN, Dann P, Stewart AF, Watson CJ, Pollak M, Karaplis AC, Wysolmerski JJ. Mammary-specific deletion of parathyroid hormone–related protein preserves bone mass during lactation. Journal Of Clinical Investigation 2003, 112: 1429-1436. PMID: 14597768, PMCID: PMC228471, DOI: 10.1172/jci19504.Peer-Reviewed Original ResearchConceptsBone lossBone turnoverMammary epithelial cellsParathyroid hormone-related proteinMammary glandMammary-specific deletionPTHrP-knockout miceRapid bone lossEpithelial cellsDihydroxy vitamin DNegative calcium balanceHormone-related proteinPreserves bone massAbsence of PTHrPExpression of CreUrinary cAMPVitamin DBone resorptionLate pregnancyBone massPTHrP mRNACalcium balanceKnockout micePTHrP proteinMammary developmentLow Estrogen and High Parathyroid Hormone-Related Peptide Levels Contribute to Accelerated Bone Resorption and Bone Loss in Lactating Mice
VanHouten JN, Wysolmerski JJ. Low Estrogen and High Parathyroid Hormone-Related Peptide Levels Contribute to Accelerated Bone Resorption and Bone Loss in Lactating Mice. Endocrinology 2003, 144: 5521-5529. PMID: 14500568, DOI: 10.1210/en.2003-0892.Peer-Reviewed Original ResearchConceptsBone lossBone mineral densityBone resorptionMineral densityDual-energy X-ray absorptiometryBone resorption markersX-ray absorptiometryRegulation of calciumAge-matched virginsPamidronate treatmentPTHrP levelsResorption markersLow estrogenEstrogen deficiencyBone turnoverEstrogen levelsPregnant miceBone metabolismBone massPeptide levelsSkeletal metabolismTotal bodyBone volumeCalcium homeostasisBiochemical markers
2002
Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*
Wysolmerski JJ, Dann PR, Zelazny E, Dunbar ME, Insogna KL, Guise TA, Perkins AS. Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*. Journal Of Bone And Mineral Research 2002, 17: 1164-1170. PMID: 12096830, DOI: 10.1359/jbmr.2002.17.7.1164.Peer-Reviewed Original ResearchConceptsBone metastasesBreast cancer cellsCancer cellsTransgenic miceTumor-bearing transgenic miceParathyroid hormone-related proteinPrimary breast cancerProduction of PTHrPHormone-related proteinWild-type littermatesEffects of PTHrPCause hypercalcemiaWild-type controlsVisceral metastasesSkeletal metastasesParathyroid hormoneBone resorptionArterial circulationBreast cancerDMBA treatmentMammary carcinogenImmunodeficient miceMammary tumorigenesisMurine modelHigh incidenceThe Evolutionary Origins of Maternal Calcium and Bone Metabolism During Lactation
Wysolmerski JJ. The Evolutionary Origins of Maternal Calcium and Bone Metabolism During Lactation. Journal Of Mammary Gland Biology And Neoplasia 2002, 7: 267-276. PMID: 12751891, DOI: 10.1023/a:1022800716196.BooksConceptsLower vertebratesEvolutionary originEutherian mammalsBone metabolismBone resorptionMaternal adaptationDifferent speciesMammalsMaternal calcium homeostasisRenal calcium excretionVertebratesAbsorption of calciumCalcium homeostasisEgg productionMetabolismMaternal calciumCalcium excretionHuman pregnancyMaternal transferCalcium metabolismFetal growthMineral metabolismNursing mothersAdaptationPregnancy
2001
PARAMETERS OF HIGH BONE-TURNOVER PREDICT BONE LOSS IN RENAL TRANSPLANT PATIENTS: A LONGITUDINAL STUDY1,2
Cruz D, Wysolmerski J, Brickel H, Gundberg C, Simpson C, Mitnick M, Kliger A, Lorber M, Basadonna G, Friedman A, Insogna K, Bia M. PARAMETERS OF HIGH BONE-TURNOVER PREDICT BONE LOSS IN RENAL TRANSPLANT PATIENTS: A LONGITUDINAL STUDY1,2. Transplantation 2001, 72: 83-88. PMID: 11468539, DOI: 10.1097/00007890-200107150-00017.Peer-Reviewed Original ResearchConceptsBone mineral densityPosttransplant bone lossRenal transplant recipientsLong-term renal transplant recipientsDual-energy X-ray absorptiometryRenal transplant patientsBone lossTransplant recipientsBone resorptionBiochemical markersTransplant patientsLumbar spineLong-term renal transplant patientsEnergy X-ray absorptiometryAccelerated bone resorptionElevated urinary levelsUse of cyclosporineElevated biochemical markersPrevious cross-sectional studiesCross-sectional studyX-ray absorptiometryStable bone massPostrenal transplantationAntiresorptive therapyKidney transplantation
2000
POSTTRANSPLANT BONE DISEASE: EVIDENCE FOR A HIGH BONE RESORPTION STATE
Cayco A, Wysolmerski J, Simpson C, Mitnick M, Gundberg C, Kliger A, Lorber M, Silver D, Basadonna G, Friedman A, Insogna K, Cruz D, Bia M. POSTTRANSPLANT BONE DISEASE: EVIDENCE FOR A HIGH BONE RESORPTION STATE. Transplantation 2000, 70: 1722-1728. PMID: 11152104, DOI: 10.1097/00007890-200012270-00011.Peer-Reviewed Original ResearchConceptsLong-term renal transplant recipientsRenal transplant recipientsBone mineral densityTransplant recipientsBone lossBone resorptionFirst post-transplant yearCumulative prednisone doseElevated urinary levelsIntact parathyroid hormonePercent of patientsDuration of dialysisPost-transplant yearPrevalence of osteoporosisCross-sectional studyLoss of boneBone resorption statePrednisone doseYear posttransplantIntact PTHRenal transplantLevels of calciumRenal functionSerum levelsTransplant year
1994
HYPERCALCEMIA OF MALIGNANCY: The Central Role of Parathyroid Hormone-Related Protein
Wysolmerski J, Broadus A. HYPERCALCEMIA OF MALIGNANCY: The Central Role of Parathyroid Hormone-Related Protein. Annual Review Of Medicine 1994, 45: 189-200. PMID: 8198376, DOI: 10.1146/annurev.med.45.1.189.Peer-Reviewed Original ResearchConceptsLocal osteolytic hypercalcemiaMalignancy-associated hypercalcemiaHormone-related protein gene expressionParathyroid hormone-related proteinCommon metabolic complicationCommon clinical problemLocal paracrine factorsHormone-related proteinParathyroid hormone-related protein gene expressionHHM syndromeMetabolic complicationsHumoral hypercalcemiaParathyroid hormoneBone resorptionHypercalcemiaParacrine roleClinical problemParacrine factorsSyndromeRecent dataProtein gene expressionHormoneMolecular mechanismsGene expressionComplications