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Effects of Drugs on Bone Quality

  • Bone quality
  • Published:
Clinical Reviews in Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

The term bone quality refers to factors that define bone mechanical strength and hence its fracture risk, either inclusive or exclusive of the quantity of mineralized tissue present. These factors include: bone size, density, shape (microarchitecture, geometry, remodeling cavity number size and distribution), porosity, mineral and collagen distribution and alignment, amount and distribution of microdamage, mineral composition, collagen cross-linking and other material properties. In this review, we will consider how pharmaceuticals used to treat osteoporosis (anabolic and catabolic agents) and those used for other conditions that affect bone quality and induce “secondary osteoporosis” alter these parameters. Observed effects vary with different methods of drug delivery, length and periodicity of use, other drugs used concomitantly or consecutively, user gender, methods of analysis and, most importantly, the genetic background of the species tested. We suggest that while increases in quantity of mineralized tissue present account for much of the reported reduction in fracture risk, drugs that correct the composition and microarchitecture of the bone, returning it to its preosteoporotic status, may provide additional benefits.

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Abbreviations

AEDS:

Enzyme-inducing antiepileptic drugs

AFF:

Atypical femoral fractures

AGE:

Advanced glycation end products

ASBMR:

American Society for Bone and Mineral Research

BMD:

Bone mineral density

BMDD:

Bone mineral density distribution

BV/TV:

Bone volume fraction

Ca/P:

Calcium-to-phosphate molar ratio

Cat K :

Cathepsin K

CO3/PO4:

Carbonate-to-phosphate ratio

COPD:

Chronic obstructive pulmonary disease

Ct. Th:

Cortical thickness

Ct. Por:

Cortical porosity

CTX:

Carboxy terminal cross-links

CYP2R:

Vitamin D hydroxylase also known as cytochrome P450 2R1

DBP:

Vitamin D-binding protein

DKK:

Dickkopf transcription factor

FDA:

Federal Drug Administration

FEM:

Finite element methods or finite element analysis

FLEX/FIT:

Fracture Intervention Trial Long-Term Extension/Fracture Intervention Trial

FREEDOM:

Fracture Reduction Evaluation of Denosumab in Osteoporosis

FTIRI:

Fourier transform infrared imaging

HIV:

Human immunodeficiency virus (AIDS)

HORIZON-PFT:

Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly–Pivotal Fracture Trial

HPO4:

Acid phosphate substitution

HRpQCT:

High-resolution peripheral quantitative computed tomography

HRT:

Hormone replacement therapy

IGF-I:

Insulin-like growth factor-1

LOFT:

Long-term Odanacatib Fracture Trial

LRP5/6:

Low-density lipoprotein receptor-related protein 5/6

MAP:

Kinase mitogen-activated protein kinase

NSAID:

Non-steroidal anti-inflammatory drugs

NMR:

Nuclear magnetic resonance

NTX:

N-terminal cross-links

ODS:

Osteogenic disorder Shionogi

OPG:

Osteoprotegerin

PERK:

ER stress-activated eIF2α kinase

PROOF:

PRevent Occurrence of Osteoporotic Fractures

PTH:

Parathyroid hormone

PTHrP:

Parathyroid hormone-related peptide

RA:

Rheumatoid arthritis

RANK:

Receptor activator of nuclear factor-kappa B

RANKL:

Receptor activator of nuclear factor-kappa B ligand

Ris/Zn-HA:

Risedronate/zinc hydroxyapatite composite

SARMS:

Selective androgen receptor modulators

SERMS:

Selective estrogen receptor modulators

Scl-Ab:

Sclerostin antibody

s-FRP1:

Secreted frizzled-related protein 1

siRNA:

Silencing RNA

SOST:

Sclerostin gene

SR:

Strontium ranelate

SSRIs:

Specific serotonin uptake inhibitors

Tb.Th:

Trabecular thickness

Tb.N:

Trabecular number

Tb.Pf:

Trabecular pattern factor

Tb.Sp:

Trabecular separation

TGF:

Transforming growth factor

TSH:

Thyroid-stimulating hormone

vBMD:

Volumetric bone mineral density

VDR:

Vitamin D receptor

Wnt:

Wingless transcription factor

XLR:

Collagen cross-link ratio

XST:

Crystallinity

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Acknowledgments

The authors appreciate the editorial comments of Dr. Judah Gerstein, Dr. David Burr and Dr. Eve Donnelly.

Funding

The authors’ research described in this manuscript was supported by NIH Grant AR041325.

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  1. Musculoskeletal Integrity Program, Hospital for Special Surgery Research Institute, 535 E 70th St, New York, NY, 10021, USA

    Laurianne Imbert & Adele Boskey

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  1. Laurianne Imbert
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  2. Adele Boskey
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Correspondence to Adele Boskey.

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Dr. Boskey declares that she has no conflicts of interest. Dr Imbert declares that she has no conflict of interest.

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All reported review data were obtained following all applicable international, national and/or institutional guidelines for the care and use of animals. All procedures reviewed in studies involving human participants were in accordance with the ethical standards of the institution and/or the appropriate governmental authorities and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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This article does not include any studies with human or animal subjects performed by the author.

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Imbert, L., Boskey, A. Effects of Drugs on Bone Quality. Clinic Rev Bone Miner Metab 14, 167–196 (2016). https://doi.org/10.1007/s12018-016-9220-6

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