Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix mineral composition or maturation.
Intermittent administration of parathyroid hormone (PTH) is used to stimulate bone formation in patients with osteoporosis. A reduction in the degree of matrix mineralisation has been reported during treatment, which may reflect either production of undermineralised matrix or a greater proportion of new matrix within the bone samples assessed. To explore these alternatives, high resolution synchrotron-based Fourier Transform Infrared Microspectroscopy (sFTIRM) coupled with calcein labelling was used in a region of non-remodelling cortical bone to determine bone composition during anabolic PTH treatment compared with region-matched samples from controls. 8week old male C57BL/6 mice were treated with vehicle or 50μg/kg PTH, 5 times/week for 4weeks (n=7-9/group). Histomorphometry confirmed greater trabecular and periosteal bone formation and 3-point bending tests confirmed greater femoral strength in PTH-treated mice. Dual calcein labels were used to match bone regions by time-since-mineralisation (bone age) and composition was measured by sFTIRM in six 15μm2regions at increasing depth perpendicular to the most immature bone on the medial periosteal edge; this allowed in situ measurement of progressive changes in bone matrix during its maturation. The sFTIRM method was validated in vehicle-treated bones where the expected progressive increases in mineral:matrix ratio and collagen crosslink type ratio were detected with increasing bone maturity. We also observed a gradual increase in carbonate content that strongly correlated with an increase in longitudinal stretch of the collagen triple helix (amide I:amide II ratio). PTH treatment did not alter the progressive changes in any of these parameters from the periosteal edge through to the more mature bone. These data provide new information about how the bone matrix matures in situ and confirm that bone deposited during PTH treatment undergoes normal collagen maturation and normal mineral accrual.
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia; The University of Melbourne, Department of Medicine at St. Vincent's Hospital, Fitzroy, Victoria, Australia.
Christina
C
Vrahnas
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia; The University of Melbourne, Department of Medicine at St. Vincent's Hospital, Fitzroy, Victoria, Australia.
Thomas A
TA
Pearson
School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.
Athena R
AR
Brunt
School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.
Mark R
MR
Forwood
Australian Synchrotron, Clayton, Victoria, Australia.
Keith R
KR
Bambery
Australian Synchrotron, Clayton, Victoria, Australia.
Mark J
MJ
Tobin
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia; The University of Melbourne, Department of Medicine at St. Vincent's Hospital, Fitzroy, Victoria, Australia.
T John
TJ
Martin
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia; The University of Melbourne, Department of Medicine at St. Vincent's Hospital, Fitzroy, Victoria, Australia. Electronic address: nsims@svi.edu.au.
Natalie A
NA
Sims
D000365:Age Determination by Skeleton; D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects*; D001857:Bone Matrix / Q000187:drug effects / Q000502:physiology*; D002113:Calcification, Physiologic / Q000187:drug effects; D000071556:Cancellous Bone / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D015591:Microspectrophotometry; D008903:Minerals / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010521:Periosteum / Q000187:drug effects / Q000502:physiology; D017550:Spectroscopy, Fourier Transform Infrared; D017356:Synchrotrons; D013977:Tibia / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000502:physiology
D045930:Anabolic Agents; D008903:Minerals; D010281:Parathyroid Hormone; D003094:Collagen