Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Current Osteoporosis Reports
Published in: Current Osteoporosis Reports 4/2015

01-08-2015 | Bone and Joint Pain (PW Mantyh and TJ Schnitzer, Section Editors)

Mechanisms and Mediators That Drive Arthritis Pain

Authors: Eugene Krustev, Danielle Rioux, Jason J. McDougall

Published in: Current Osteoporosis Reports | Issue 4/2015

Login to get access

Abstract

There are over 100 different types of arthritis and each can differ greatly in their aetiology and pathophysiology; however, one characteristic that is common to all arthritic conditions is joint pain. Musculoskeletal pain is the leading cause of disability in the world, and the number one reason arthritis patients visit their primary care physician. Despite the prevalence and burden of arthritis pain, current analgesics lack sufficient efficacy and are plagued by multiple adverse side effects. In this review, we outline the current landscape of research concerning joint pain, drawing from both preclinical and clinical studies. Specifically, this review is a discussion of the different neurophysiological processes that occur during joint disease and how inflammatory and neuropathic aspects contribute to the development of arthritis pain.
Literature
1.
March L, Smith EUR, Hoy DG, Cross MJ, Sanchez-Riera L, Blyth F, et al. Burden of disability due to musculoskeletal (MSK) disorders. Best Pract Res Clin Rheumatol. 2014;28:353–66.PubMedCrossRef
2.
Heppelmann B, Schaible HG. Origin of sympathetic innervation of the knee joint in the cat: a retrograde tracing study with horseradish peroxidase. Neurosci Lett. 1990;108:71–5.PubMedCrossRef
3.
McDougall JJ. Abrogation of alpha-adrenergic vasoactivity in chronically inflamed rat knee joints. Am J Physiol Regul Integr Comp Physiol. 2001;281:R821–7.
4.
McDougall JJ, Karimian SM, Ferrell WR. Prolonged alteration of vasoconstrictor and vasodilator responses in rat knee joints by adjuvant monoarthritis. Exp Physiol. 1995;80:349–57.PubMedCrossRef
5.
Freeman MA, Wyke B. The innervation of the knee joint. An anatomical and histological study in the cat. J Anat. 1967;101:505–32.PubMedCentralPubMed
6.
Hildebrand C, Oqvist G, Brax L, Tuisku F. Anatomy of the rat knee joint and fibre composition of a major articular nerve. Anat Rec. 1991;229:545–55.PubMedCrossRef
7.
8.
Heppelmann B, Messlinger K, Neiss WF, Schmidt RF. Ultrastructural three-dimensional reconstruction of group III and group IV sensory nerve endings (“free nerve endings”) in the knee joint capsule of the cat: evidence for multiple receptive sites. J Comp Neurol. 1990;292:103–16.PubMedCrossRef
9.
Heppelmann B, McDougall JJ. Inhibitory effect of amiloride and gadolinium on fine afferent nerves in the rat knee: evidence of mechanogated ion channels in joints. Exp Brain Res. 2005;167:114–8.PubMedCrossRef
10.
11.
Aggarwal R, Liao K, Nair R, Ringold S, Costenbader KH. Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid arthritis. Arthritis Rheum. 2009;61:1472–83.PubMedCentralPubMedCrossRef
12.
McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7:429–42.PubMedCrossRef
13.
Eyre DR. Collagens and cartilage matrix homeostasis. Clin Orthop Relat Res. 2004;S118–22.
14.
Houard X, Goldring MB, Berenbaum F. Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr Rheumatol Rep. 2013;15:375.PubMedCentralPubMedCrossRef
15.
16.
Gold MS, Levine JD, Correa AM. Modulation of TTX-R INa by PKC and PKA and their role in PGE2-induced sensitization of rat sensory neurons in vitro. J Neurosci. 1998;18:10345–55.PubMed
17.
Pulichino A-M, Rowland S, Wu T, Clark P, Xu D, Mathieu M-C, et al. Prostacyclin antagonism reduces pain and inflammation in rodent models of hyperalgesia and chronic arthritis. J Pharmacol Exp Ther. 2006;319:1043–50.PubMedCrossRef
18.
19.
Farahat MN, Yanni G, Poston R, Panayi GS. Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis. 1993;52:870–5.PubMedCentralPubMedCrossRef
20.
Smith MD, Triantafillou S, Parker A, Youssef PP, Coleman M. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol. 1997;24:365–71.PubMed
21.
Orita S, Ishikawa T, Miyagi M, Ochiai N, Inoue G, Eguchi Y, et al. Pain-related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain. BMC Musculoskelet Disord. 2011;12:134.PubMedCentralPubMedCrossRef
22.
Lewthwaite J, Blake S, Hardingham T, Foulkes R, Stephens S, Chaplin L, et al. Role of TNF alpha in the induction of antigen induced arthritis in the rabbit and the anti-arthritic effect of species specific TNF alpha neutralising monoclonal antibodies. Ann Rheum Dis. 1995;54:366–74.PubMedCentralPubMedCrossRef
23.
Szekanecz Z, Halloran MM, Volin MV, Woods JM, Strieter RM, Kenneth Haines G, et al. Temporal expression of inflammatory cytokines and chemokines in rat adjuvant-induced arthritis. Arthritis Rheum. 2000;43:1266–77.PubMedCrossRef
24.
Tonussi CR, Ferreira SH. Tumour necrosis factor-alpha mediates carrageenin-induced knee-joint incapacitation and also triggers overt nociception in previously inflamed rat knee-joints. Pain. 1999;82:81–7.PubMedCrossRef
25.
Schaible H-G, von Banchet GS, Boettger MK, Bräuer R, Gajda M, Richter F, et al. The role of proinflammatory cytokines in the generation and maintenance of joint pain. Ann N Y Acad Sci. 2010;1193:60–9.PubMedCrossRef
26.
Hensellek S, Brell P, Schaible H-G, Bräuer R, Segond von Banchet G. The cytokine TNFalpha increases the proportion of DRG neurones expressing the TRPV1 receptor via the TNFR1 receptor and ERK activation. Mol Cell Neurosci. 2007;36:381–91.PubMedCrossRef
27.
Ebbinghaus M, Uhlig B, Richter F, von Banchet GS, Gajda M, Bräuer R, et al. The role of interleukin-1β in arthritic pain: main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis. Arthritis Rheum. 2012;64:3897–907.PubMedCrossRef
28.
Obreja O, Biasio W, Andratsch M, Lips KS, Rathee PK, Ludwig A, et al. Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons. Brain. 2005;128:1634–41.PubMedCrossRef
29.
Von Banchet GS, Kiehl M, Schaible H-G. Acute and long-term effects of IL-6 on cultured dorsal root ganglion neurones from adult rat. J Neurochem. 2005;94:238–48.CrossRef
30.•
Segond von Banchet G, Boettger MK, König C, Iwakura Y, Bräuer R, Schaible H-G. Neuronal IL-17 receptor upregulates TRPV4 but not TRPV1 receptors in DRG neurons and mediates mechanical but not thermal hyperalgesia. Mol Cell Neurosci. 2013;52:152–60. In this study, the potential role of IL-17 in neuronal sensitization was uncovered. Furthermore, these results suggest that TRPV4 may also play an important role in nociceptor sensitization.
31.
Lam FY, Ferrell WR. CGRP modulates nerve-mediated vasoconstriction of rat knee joint blood vessels. Ann N Y Acad Sci. 1992;657:519–21.PubMedCrossRef
32.
McDougall JJ, Barin AK. The role of joint nerves and mast cells in the alteration of vasoactive intestinal peptide (VIP) sensitivity during inflammation progression in rats. Br J Pharmacol. 2005;145:104–13.PubMedCentralPubMedCrossRef
33.
Lembeck F, Holzer P. Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn Schmiedebergs Arch Pharmacol. 1979;310:175–83.PubMedCrossRef
34.
Goebeler M, Henseleit U, Roth J, Sorg C. Substance P and calcitonin gene-related peptide modulate leukocyte infiltration to mouse skin during allergic contact dermatitis. Arch Dermatol Res. 1994;286:341–6.PubMedCrossRef
35.
Heppelmann B, Pawlak M. Sensitisation of articular afferents in normal and inflamed knee joints by substance P in the rat. Neurosci Lett. 1997;223:97–100.PubMedCrossRef
36.
McDougall JJ, Watkins L, Li Z. Vasoactive intestinal peptide (VIP) is a modulator of joint pain in a rat model of osteoarthritis. Pain. 2006;123:98–105.PubMedCrossRef
37.
Schuelert N, McDougall JJ. Electrophysiological evidence that the vasoactive intestinal peptide receptor antagonist VIP6-28 reduces nociception in an animal model of osteoarthritis. Osteoarthritis Cartilage. 2006;14:1155–62.PubMedCrossRef
38.
McDougall JJ, Schuelert N. Age alters the ability of substance P to sensitize joint nociceptors in guinea pigs. J Mol Neurosci. 2007;31:289–96.PubMed
39.
Li Z, Proud D, Zhang C, Wiehler S, McDougall JJ. Chronic arthritis down-regulates peripheral mu-opioid receptor expression with concomitant loss of endomorphin 1 antinociception. Arthritis Rheum. 2005;52:3210–9.PubMedCrossRef
40.
Bär K-J, Schurigt U, Scholze A, Segond Von Banchet G, Stopfel N, Bräuer R, et al. The expression and localization of somatostatin receptors in dorsal root ganglion neurons of normal and monoarthritic rats. Neuroscience. 2004;127:197–206.PubMedCrossRef
41.
Carlton SM, Du J, Davidson E, Zhou S, Coggeshall RE. Somatostatin receptors on peripheral primary afferent terminals: inhibition of sensitized nociceptors. Pain. 2001;90:233–44.PubMedCrossRef
42.
Kawabata A, Kawao N, Kuroda R, Tanaka A, Shimada C. The PAR-1-activating peptide attenuates carrageenan-induced hyperalgesia in rats. Peptides. 2002;23:1181–3.PubMedCrossRef
43.
Russell FA, Schuelert N, Veldhoen VE, Hollenberg MD, McDougall JJ. Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint. Br J Pharmacol. 2012;167:1665–78.PubMedCentralPubMedCrossRef
44.
Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi S, Ennes HS, et al. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med. 2000;6:151–8.PubMedCrossRef
45.
Vergnolle N, Bunnett NW, Sharkey KA, Brussee V, Compton SJ, Grady EF, et al. Proteinase-activated receptor-2 and hyperalgesia: a novel pain pathway. Nat Med. 2001;7:821–6.PubMedCrossRef
46.
McDougall JJ, Zhang C, Cellars L, Joubert E, Dixon CM, Vergnolle N. Triggering of proteinase-activated receptor 4 leads to joint pain and inflammation in mice. Arthritis Rheum. 2009;60:728–37.PubMedCrossRef
47.
Ware MA, Adams H, Guy GW. The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract. 2005;59:291–5.PubMedCrossRef
48.
Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2008;10:R43.PubMedCentralPubMedCrossRef
49.
McDougall JJ. Cannabinoids and pain control in the periphery. In: Cairns BE, editor. Peripheral receptor for targets analgesia. 1st ed. Hoboken, New Jersey: Wiley; 2009. pp. 325–46.
50.
Krustev E, Reid A, McDougall JJ. Tapping into the endocannabinoid system to ameliorate acute inflammatory flares and associated pain in mouse knee joints. Arthritis Res Ther. 2014;16:437.PubMedCentralPubMedCrossRef
51.••
Schuelert N, Johnson MP, Oskins JL, Jassal K, Chambers MG, McDougall JJ. Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis. Pain. 2011;152:975–81. This paper provided the first preclinical evidence that joints possess an endocannabinoid system that can offset osteoarthritis pain.
52.
Schuelert N, McDougall JJ. Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum. 2008;58:145–53.PubMedCrossRef
53.
Mecs L, Tuboly G, Toth K, Nagy E, Nyari T, Benedek G, et al. Peripheral antinociceptive effect of 2-arachidonoyl-glycerol and its interaction with endomorphin-1 in arthritic rat ankle joints. Clin Exp Pharmacol Physiol. 2010;37:544–50.PubMedCrossRef
54.
Kinsey SG, Naidu PS, Cravatt BF, Dudley DT, Lichtman AH. Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice. Pharmacol Biochem Behav. 2011;99:718–25.PubMedCentralPubMedCrossRef
55.
Huggins JP, Smart TS, Langman S, Taylor L, Young T. An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of th. Pain. 2012;153:1837–46.PubMedCrossRef
56.
Gauldie SD, McQueen DS, Pertwee R, Chessell IP. Anandamide activates peripheral nociceptors in normal and arthritic rat knee joints. Br J Pharmacol. 2001;132:617–21.PubMedCentralPubMedCrossRef
57.••
Hochman JR, Gagliese L, Davis AM, Hawker GA. Neuropathic pain symptoms in a community knee OA cohort. Osteoarthritis Cartilage. 2011;19:647–54. This study provided some of the first clinical evidence highlighting a potential neuropathic component of OA pain.
58.
Treede R-D, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–5.PubMedCrossRef
59.
McDougall JJ, Bray RC, Sharkey KA. Morphological and immunohistochemical examination of nerves in normal and injured collateral ligaments of rat, rabbit, and human knee joints. Anat Rec. 1997;248:29–39.PubMedCrossRef
60.
Suri S, Gill SE, Massena de Camin S, Wilson D, McWilliams DF, Walsh DA. Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis. Ann Rheum Dis. 2007;66:1423–8.PubMedCentralPubMedCrossRef
61.
Ivanavicius SP, Ball AD, Heapy CG, Westwood FR, Murray F, Read SJ. Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: increased expression of ATF-3 and pharmacological characterisation. Pain. 2007;128:272–82.PubMedCrossRef
62.
Obata K, Yamanaka H, Fukuoka T, Yi D, Tokunaga A, Hashimoto N, et al. Contribution of injured and uninjured dorsal root ganglion neurons to pain behavior and the changes in gene expression following chronic constriction injury of the sciatic nerve in rats. Pain. 2003;101:65–77.PubMedCrossRef
63.
McDougall JJ, Andruski B, Schuelert N, Hallgrímsson B, Matyas JR. Unravelling the relationship between age, nociception and joint destruction in naturally occurring osteoarthritis of Dunkin Hartley guinea pigs. Pain. 2009;141:222–32.PubMedCrossRef
64.
Parks EL, Geha PY, Baliki MN, Katz J, Schnitzer TJ, Apkarian AV. Brain activity for chronic knee osteoarthritis: dissociating evoked pain from spontaneous pain. Eur J Pain. 2011;15:843.e1–14.
65.
Luo ZD, Chaplan SR, Higuera ES, Sorkin LS, Stauderman KA, Williams ME, et al. Upregulation of dorsal root ganglion (alpha)2(delta) calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci. 2001;21:1868–75.PubMed
66.
Nieto-Rostro M, Sandhu G, Bauer CS, Jiruska P, Jefferys JGR, Dolphin AC. Altered expression of the voltage-gated calcium channel subunit α2δ-1: a comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain. Neuroscience. 2014;283:124–37.PubMedCentralPubMedCrossRef
67.
Uchitel OD, Di Guilmi MN, Urbano FJ, Gonzalez-Inchauspe C. Acute modulation of calcium currents and synaptic transmission by gabapentinoids. Channels (Austin). 2010;4:490–6.
68.
Hanesch U, Pawlak M, McDougall JJ. Gabapentin reduces the mechanosensitivity of fine afferent nerve fibres in normal and inflamed rat knee joints. Pain. 2003;104:363–6.PubMedCrossRef
69.
Fernihough J, Gentry C, Malcangio M, Fox A, Rediske J, Pellas T, et al. Pain related behaviour in two models of osteoarthritis in the rat knee. Pain. 2004;112:83–93.PubMedCrossRef
70.••
Schuelert N, McDougall JJ. Involvement of Nav 1.8 sodium ion channels in the transduction of mechanical pain in a rodent model of osteoarthritis. Arthritis Res Ther. 2012;14:R5. The first report that nociceptor-specific sodium channels could be used as a target for reducing osteoarthritis pain.
71.
Shinder V, Govrin-Lippmann R, Cohen S, Belenky M, Ilin P, Fried K, et al. Structural basis of sympathetic-sensory coupling in rat and human dorsal root ganglia following peripheral nerve injury. J Neurocytol. 1999;28:743–61.PubMedCrossRef
72.
Birder LA, Perl ER. Expression of alpha2-adrenergic receptors in rat primary afferent neurones after peripheral nerve injury or inflammation. J Physiol. 1999;515:533–42.
73.
74.
75.
Lee K-F, Li E, Huber LJ, Landis SC, Sharpe AH, Chao MV, et al. Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell. 1992;69:737–49.PubMedCrossRef
76.
Scarpini E, Ross AH, Rosen JL, Brown MJ, Rostami A, Koprowski H, et al. Expression of nerve growth factor receptor during human peripheral nerve development. Dev Biol. 1988;125:301–10.PubMedCrossRef
77.
Wild KD, Bian D, Zhu D, Davis J, Bannon AW, Zhang TJ, et al. Antibodies to nerve growth factor reverse established tactile allodynia in rodent models of neuropathic pain without tolerance. J Pharmacol Exp Ther. 2007;322:282–7.PubMedCrossRef
78.
Shelton DL, Zeller J, Ho W-H, Pons J, Rosenthal A. Nerve growth factor mediates hyperalgesia and cachexia in auto-immune arthritis. Pain. 2005;116:8–16.PubMedCrossRef
79.
Mardy S, Miura Y, Endo F, Matsuda I, Sztriha L, Frossard P, et al. Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor. Am J Hum Genet. 1999;64:1570–9.PubMedCentralPubMedCrossRef
80.
Tal M, Liberman R. Local injection of nerve growth factor (NGF) triggers degranulation of mast cells in rat paw. Neurosci Lett. 1997;221:129–32.PubMedCrossRef
81.
Shu X, Mendell LM. Nerve growth factor acutely sensitizes the response of adult rat sensory neurons to capsaicin. Neurosci Lett. 1999;274:159–62.PubMedCrossRef
82.
Zhang Y, Moheban DB, Conway BR, Bhattacharyya A, Segal RA. Cell surface Trk receptors mediate NGF-induced survival while internalized receptors regulate NGF-induced differentiation. J Neurosci. 2000;20:5671–8.PubMed
83.
Lindsay RM, Harmar AJ. Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature. 1989;337:362–4.PubMedCrossRef
84.
Kerr BJ, Souslova V, McMahon SB, Wood JN. A role for the TTX-resistant sodium channel Nav 1.8 in NGF-induced hyperalgesia, but not neuropathic pain. Neuroreport. 2001;12:3077–80.PubMedCrossRef
85.
Balanescu AR, Feist E, Wolfram G, Davignon I, Smith MD, Brown MT, et al. Efficacy and safety of tanezumab added on to diclofenac sustained release in patients with knee or hip osteoarthritis: a double-blind, placebo-controlled, parallel-group, multicentre phase III randomised clinical trial. Ann Rheum Dis. 2014;73:1665–72.PubMedCrossRef
86.
Spierings ELH, Fidelholtz J, Wolfram G, Smith MD, Brown MT, West CR. A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee. Pain. 2013;154:1603–12.PubMedCrossRef
87.
Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR. Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind, placebo-controlled phase III trial. Arthritis Rheum. 2013;65:1795–803.PubMedCrossRef
88.
Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR. Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial. J Pain. 2012;13:790–8.PubMedCrossRef
89.
Nagashima H, Suzuki M, Araki S, Yamabe T, Muto C. Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study. Osteoarthritis Cartilage. 2011;19:1405–12.PubMedCrossRef
90.
Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL, Smith MD, et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010;363:1521–31.PubMedCrossRef
91.
Schnitzer TJ, Lane NE, Birbara C, Smith MD, Simpson SL, Brown MT. Long-term open-label study of tanezumab for moderate to severe osteoarthritic knee pain. Osteoarthritis Cartilage. 2011;19:639–46.PubMedCrossRef
92.
Andreev NY, Dimitrieva N, Koltzenburg M, McMahon SB. Peripheral administration of nerve growth factor in the adult rat produces a thermal hyperalgesia that requires the presence of sympathetic post-ganglionic neurones. Pain. 1995;63:109–15.PubMedCrossRef
93.
Dyck PJ, Peroutka S, Rask C, Burton E, Baker MK, Lehman KA, et al. Intradermal recombinant human nerve growth factor induces pressure allodynia and lowered heat-pain threshold in humans. Neurology. 1997;48:501–5.PubMedCrossRef
Metadata
Title
Mechanisms and Mediators That Drive Arthritis Pain
Authors
Eugene Krustev
Danielle Rioux
Jason J. McDougall
Publication date
01-08-2015
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 4/2015
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-015-0275-y

Other articles of this Issue 4/2015

Current Osteoporosis Reports 4/2015 Go to the issue

Nutrition, Exercise, and Lifestyle in Osteoporosis (CM Weaver and R Daly, Section Editors)

Dietary Approaches for Bone Health: Lessons from the Framingham Osteoporosis Study

Kidney and Bone (SM Moe and IB Salusky, Section Editors)

Molecular Mechanisms of Vascular Calcification in Chronic Kidney Disease: The Link between Bone and the Vasculature

Nutrition, Exercise, and Lifestyle in Osteoporosis (CM Weaver and R Daly, Section Editors)

The Role of B-Vitamins in Bone Health and Disease in Older Adults

Skeletal Biology and Regulation (MR Forwood and A Robling, Section Editors)

The Vestibular System: A Newly Identified Regulator of Bone Homeostasis Acting Through the Sympathetic Nervous System

Osteocytes (T Bellido and J Klein-Nulend, Section Editors)

Osteocytes and Homeostasis of Remote Organs

Nutrition, Exercise, and Lifestyle in Osteoporosis (CM Weaver and R Daly, Section Editors)

Fall and Fracture Risk in Sarcopenia and Dynapenia With and Without Obesity: the Role of Lifestyle Interventions