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FRI0566 Teriparatide and alendronate improved bone loss and hyperalgesia in a mouse model of osteoporosis
  1. N Nagao,
  2. H Wakabayashi,
  3. S Kato,
  4. G Miyamura,
  5. Y Naito,
  6. A Sudo
  1. Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan, Tsu, Japan

Abstract

Background Osteoporosis may cause not only fractures but also chronic back pain in elderly women. Teriparatide (TPTD) and alendronate (ALN) are widely used in clinical for treatment of osteoporosis. Several studies have demonstrated that TPTD and ALN treatments improved skeletal pain in osteoporosis patients.

Objectives We investigated the effect of TPTD and ALN on pain-related behavior in ovariectomized (OVX) mice. And we investigated expression of inflammatory cytokines treated OVX mice.

Methods 8-week-old female ddY mice were OVX and assigned to 4groups; SHAM-operated mice treated with vehicle (SHAM), OVX mice treated with vehicle (OVX), OVX mice treated with TPTD (TPTD) and OVX mice treated with ALN (ALN). Mice were started treatment immediately after surgery. For 4 weeks, mice were injected subcutaneously with vehicle or 40μg/kg ALN twice a week or 40μg/kg TPTD 5 times a week.

The bilateral distal femur metaphyses were analyzed three-dimensionally by μCT 4 weeks after surgery (each group; n=8).

Mechanical sensitivity was tested using von Frey filaments 4 weeks after surgery. To evaluate the 50% withdrawal threshold, seven von Frey filaments with forces of 0.07, 0.16, 0.4, 0.6, 1.0, 1.4 and 2.0 g were applied to the middle of the plantar surface. Data was collected using the up-down method.

To evaluate expression of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), mice were anesthetized and the bilateral hindlimb bone excised. We performed quantitative polymerase chain reaction (q-PCR) from hindlimb bone.

Results μCT analysis of the distal femur metaphysis showed that bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) were significantly less in the OVX group than in the SHAM group, whereas trabecular separation (Tb.Sp) was significantly greater in the OVX group than in the SHAM group. In the TPTD and ALN group, BV/TV and Tb.N were significantly greater than in the OVX group, whereas Tb.Sp was significantly less than in the OVX group. And in the ALN group, BV/TV and Tb.N were significantly greater than in the TPTD group, but Tb.Sp was no significance.

The 50% withdrawal threshold was significantly lower in the OVX group than in the SHAM group, and it was significantly higher in the TPTD and ALN group than in the OVX group. And the 50% withdrawal threshold was no significance between the TPTD and ALN group.

The expression levels of TNF-α was increased in the OVX group compared with those in the SHAM group. Other cytokines were not increased significantly in the OVX group. In the TPTD and ALN group, the expression levels of TNF-α was significantly degreased than the OVX group. And the expression levels of TNF-α was no significance between the TPTD and ALN group.

Conclusions In this study, TPTD and ALN treatments prevented bone loss in OVX mice. Mechanical hyperalgesia in hindlimbs tended to be decreased in the OVX group compared with the TPTD and ALN group. ALN treatment was more effective in bone formation compared with TPTD treatment, whereas pain relief was no significance between TPTD and ALN treatment. These results suggest that TPTD treatment was more effective in osteoporosis patients with skeletal pain.

Disclosure of Interest None declared

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