Effects of Antiresorptive Therapy on Bone Microarchitecture

Study

Drug

Duration (months)

Age (years)

Distal radius

Tb.vBMD or BV/TV

Distal radius

Ct.vBMD

Distal radius

Ct.Th

Burghardt et al. (2010)

Alendronate

56 ± 4

Placebo

56 ± 2

Rizzoli et al. (2012)

Alendronate

64 ± 8

Strontium

64 ± 8

Seeman et al. (2010)

Alendronate

61 ± 5

~+2 to 3 %^a

Denosumab

60 ± 6

~0 to +1 %^a

~0 to +0.5 %^a

~+3 to 4 %^a

Placebo

61 ± 5

~ −2 %^a

~ −1.5 %^a

~0 to −1 %^a

Chapurlat et al. (2013)^b

Ibandronate

63 ± 5

No difference between groups

Placebo

63 ± 5

Bala et al. (2014)

Risedronate (<55 year)

112

53 ± 2

−1.60 ± 4.49

Not reported

Placebo (<55 year)

53 ± 2

−3.61 ± 8.21

Not reported

Risedronate (>55 year)

109

62 ± 6

Not reported

Risedronate (>55 year)

61 ± 4

Not reported

Hansen et al. (2013)

Zoledronic acid

70 (54–86)

+2.5 ± 5.1 %

PTH(1-34)

72 (59–80)

−2.4 ± 4.5 %

+2.0 ± 3.8 %

PTH(1-84)

70 (61–86)

−3.5 ± 3.3 %

Cheung et al. (2014)

Odanacatib

109

64 ± 7

+2.57 %^a

+0.78 %^a

+1.57 %^a

Placebo

105

64 ± 6

−1.65 %^a

−5.28 %^a

Schafer et al. (2012)

Ibandronate and PTH(1-84)^c

62 ± 4

+2.26 % (1.37, 3.14)^a

−0.76 (−1.33, −0.20)^a

−1.90 (−2.61, −1.18)^a

Tsai et al. (2014)

PTH(1-34)

66 ± 8

−1.9 ± 2.8 %

Denosumab

66 ± 8

+1.3 ± 2.8 %

+0.7 ± 1.4 %

+2.3 ± 4.8

Denosumab and PTH(1-34)

66 ± 9

+3.1 ± 3.3 %

+1.0 ± 1.6 %

+2.3 ± 4.8

NS not significant

Values are means ± SD unless otherwise noted as ^aLeast squares means, and if values reported, with 95 % CIs

^bFor the Chapurlat et al. (2013) study, significance of within-group changes was not reported

^cFor the Schafer et al. (2012) study, subjects were treated with 6 months of PTH(1-84), either as one 6- or two 3-month courses, in combination with ibandronate over 2 years

Summary of within-group changes from baseline of trabecular density (trabecular vBMD or calculated BV/TV), cortical vBMD, and cortical thickness (Ct.Th) at the distal radius in HR-pQCT studies evaluating antiresorptive treatment

Table 10.2

Effect of antiresorptive therapy on trabecular and cortical density and cortical thickness at the distal tibia, as assessed in vivo by HR-pQCT

Study	Drug	Duration (months)	N	Age (years)	Distal tibia Tb.vBMD or BV/TV	Distal tibia Ct.vBMD	Distal tibia Ct.Th
Burghardt et al. (2010)	Alendronate	24	13	56 ± 4	~ +1 to 2 %	NS	~ +3 to 4 %
Burghardt et al. (2010)	Placebo	24	20	56 ± 2	NS	NS	NS
Rizzoli et al. (2012)	Alendronate	24	42	64 ± 8	NS	NS	NS
Rizzoli et al. (2012)	Strontium	24	41	64 ± 8	+2.5 ± 5.1 %	+1.4 ± 2.8 %	+6.3 ± 9.5 %
Seeman et al. (2010)	Alendronate	12	82	61 ± 5	+0.5 to 1 %^a	NS	+4 to 5 %^a
	Denosumab	12	83	60 ± 6	+1 to 1.5 %^a	+0.5 to 1 %^a	+5 to 6 %^a
	Placebo	12	82	61 ± 5	−0.5 to −1 %^a	−0.5 to −1 %^a	+1 to 2 %^a
Chapurlat et al. (2013)^b	Ibandronate	24	72	63 ± 5	No difference between groups	Greater increase in ibandronate group	Greater increase in ibandronate
Chapurlat et al. (2013)^b	Placebo	24	76	63 ± 5	No difference between groups	Greater increase in ibandronate group	Greater increase in ibandronate
Bala et al. (2014)	Risedronate (<55 year)	12	112	53 ± 2	NS	−1.09 ± 2.41	Not reported
	Placebo (<55 year)	12	49	53 ± 2	NS	NS	Not reported
	Risedronate (>55 year)	12	109	62 ± 6	NS	NS	Not reported
	Risedronate (>55 year)	12	54	61 ± 4	+0.40 ± 1.51	+0.50 ± 1.68	Not reported
Hansen et al. (2013)	Zoledronic acid	18	33	70 (54–86)	+2.2 % ± 2.2 %	+1.5 % ± 2.0	+3.0 ± 3.5 %
	PTH(1-34)	18	18	72 (59–80)	+3.3 % ± 5.7 %	−1.6 % ± 4.4	+3.8 ± 10.4 %
	PTH(1-84)	18	20	70 (61–86)	NS	−4.7 % ± 4.5	−2.8 ± 4.7 %
Cheung et al. (2014)	Odanacatib	24	109	64 ± 7	2.27 %^a	NS	+2.15 %^a
Cheung et al. (2014)	Placebo	24	105	64 ± 6	+0.84^a	−1.05 %^a	−3.03 %^a
Schafer et al. (2012)	Ibandronate and PTH(1-84)^c	24	43	62 ± 4	+3.22 % (2.35, 4.10)^a	NS	NS
Tsai et al. (2014)	PTH(1-34)	12	31	66 ± 8	NS	−1.6 % ± 1.9	NS
	Denosumab	12	33	66 ± 8	+2.1 % ± 3.0	+0.9 % ± 1.2	+3.3 % ± 3.3
	Denosumab and PTH(1-34)	12	30	66 ± 9	+1.6 % ± 2.8	+1.5 % ± 1.5	+5.4 % ± 3.9

NS not significant

Values are means ± SD unless otherwise noted as ^aLeast squares means, and if values reported, with 95 % CIs

^bFor the Chapurlat et al. (2013) study, significance of within-group changes was not reported

^cFor the Schafer et al. (2012) study, subjects were treated with 6 months of PTH(1-84), either as one 6- or two 3-month courses, in combination with ibandronate over 2 years

Summary of within-group changes from baseline for trabecular density (trabecular vBMD or calculated BV/TV), cortical vBMD, and cortical thickness (Ct.Th) at the distal tibia in HR-pQCT studies evaluating antiresorptive treatment

Effect of Antiresorptive Therapy on Trabecular Microarchitecture

Overall, the effect of antiresorptive therapy on trabecular vBMD and microarchitecture varies by treatment, skeletal site, and study. Two years of ibandronate treatment in postmenopausal women with osteopenia did not lead to significant improvement in trabecular vBMD in comparison to the placebo control group at either the distal radius or distal tibia [48]. Similarly, in a placebo-controlled study of postmenopausal women with low bone density, Burghardt et al. reported that 2 years of alendronate therapy also did not change trabecular vBMD at the distal radius [49]. This finding was also observed at the distal radius in two other studies of postmenopausal women treated with alendronate [50, 51]. However, Seeman et al. and Burghardt et al. reported an increase in trabecular vBMD at the distal tibia after 12 and 24 months of alendronate, respectively [49, 51]. Treatments with 12 months of denosumab, 18 months of zoledronic acid, and 24 months of odanacatib in postmenopausal women were all reported to increase trabecular vBMD at both skeletal sites [51–53].

Despite advancements in high-resolution imaging, changes in trabecular microarchitectural parameters in response to antiresorptive therapy have generally not been detected by HR-pQCT [48–54]. The lack of significant findings may be due to limited resolution and/or poor measurement precision relative to the expected change induced by the treatment. Although the reconstructed voxel size is 82 μm for the standard patient HR-pQCT protocol, the actual spatial resolution of the image is approximately 130–140 μm, which is about equal to the width of human trabeculae [55]. Moreover, subtle motion during the scan, more common at the radius than the tibia, can negatively affect the precision of HR-pQCT measurements thereby adding to the challenge of detecting small changes. Indeed, whereas the short-term precision of trabecular density measurements by HR-pQCT is excellent (<1 %), the short-term precision of trabecular microarchitecture measurements is substantially worse (1.8–4.4 %) [9, 10]. Though not routinely used, 3-D registration of follow-up images to the baseline image may improve the ability to detect changes in bone microstructure [56, 57].

A recently developed technique called individual trabecula segmentation (ITS) enables detailed quantification of trabecular morphology (plates or rods) and direct measurements of each individual trabecula [58]. The effect of anabolic therapy on HR-pQCT-based ITS parameters has been reported and thus may be a useful method to characterize other treatment-induced changes in trabecular microarchitecture in the future [59].

Only gold members can continue reading. Log In or Register to continue