Teriparatide in bisphosphonate-resistant osteoporosis: microarchitectural changes and clinical results after 6 and 18 months.

A number of osteoporotic patients under bisphosphonate treatment present persistent fragility fractures and bone loss despite good compliance. The objective of this 18-month prospective study was to investigate the effect of teriparatide [rhPTH(1-34)] in 25 female osteoporotics who were inadequate responders to oral bisphosphonates and to correlate microarchitectural changes in three consecutive iliac crest biopsies measured by micro-computed tomography (µCT) with bone mineral density (BMD) and bone serum markers. Scanned biopsies at baseline (M0), 6 months (M6), and 18 months (M18) demonstrated early significant (P < 0.01) increases in bone volume per tissue volume (+34%) and trabecular number (+14%) at M6 with only moderate changes in most µCT structural parameters between M6 and M18. µCT-measured bone tissue density was significantly decreased at M18, expressing an overall lower degree of tissue mineralization characteristic for new bone formation despite unchanged trabecular thickness due to increased intratrabecular tunneling at M18. µCT results were consistent with serum bone turnover markers, reaching maximal levels of bone alkaline phosphatase and serum ß-crosslaps at M6, with subsequent decline until M18. BMD assessed by DXA demonstrated persistent increases at the lumbar spine until M12, whereas no significant change was observed at the hip. Type (alendronate/risedronate) and duration (3.5 ± 4 years) of prior bisphosphonate treatment did not influence outcome on µCT, BMD, or bone marker results. The overall results indicate a positive ceiling effect of teriparatide on bone microarchitecture and bone markers after 6 and 12 months for lumbar spine BMD, with no additional gain until M18 in bisphosphonate nonresponders.

Anatomic structures involved in early- and late-stage sacroiliitis in spondylarthritis: a detailed analysis by contrast-enhanced magnetic resonance imaging.

OBJECTIVE: To localize inflammatory and chronic changes to defined areas in the sacroiliac joints in patients with early-stage compared with late-stage spondylarthritis (SpA), using magnetic resonance imaging (MRI). METHODS: Using MRI, 93 patients with SpA and inflammatory back pain who had radiographs of the sacroiliac joints were examined, comprising 31 patients with ankylosing spondylitis (AS) and 62 with other SpA subsets, including 48 with undifferentiated SpA (uSpA). MRI was performed using T1-weighted, T2*-weighted, STIR, and dynamic contrast-enhanced (gadolinium diethylenetriaminepentaacetic acid) sequences. Two readers retrospectively analyzed the images by differentiating 9 areas of the sacroiliac joints: the ventral and caudal joint capsule, cavum, subchondral bone, bone marrow, ligament entheses, and ligaments; the sacral and iliac sides were tabulated separately. RESULTS: By MRI, sacroiliitis was more often bilateral in AS (84%) than in uSpA (48%) (P = 0.01). Inflammatory changes were found in a mean +/- SD 4.7 +/- 2.9 regions/joint, with involvement of 4.5 +/- 3.2 regions in early disease versus 5.2 +/- 2.3 regions in late disease (P not significant [NS]). Involvement of the iliac side of the sacroiliac joints was found to be more frequent than the sacral side in early disease (58% versus 48%; P < 0.01) as compared with that in late disease (58% versus 63%; P NS). The dorsocaudal parts of the synovial joint and the bone marrow were the most frequently inflamed structures in early disease (P < 0.001 for ventral versus dorsal joint capsule). In contrast, involvement of the entheses was more common in advanced disease (early 43% versus late 86%; P < 0.001). Similarly, the ligaments were more frequently involved in the late stages (early 26% versus late 40%; P = 0.06). Both patterns of bone marrow inflammation (focal and diffuse) were observed in equal frequencies in early and late disease (17% and 42% versus 26% and 43%, respectively; P NS). HLA-B27-positive patients (n = 80) had more entheseal involvement than did HLA-B27-negative patients (n = 13) (60% versus 39%; P = 0.05). HLA-B27-negative patients had a shorter disease duration (2.2 years versus 4.4 years; P = 0.05) and were more often female (62%; P = 0.02). When all pathologic changes were assessed, the STIR sequence (performed in 62 patients) was less sensitive than the contrast-enhanced sequences in that it was not able to show all relevant changes in 27% of these patients (n = 17), failing to reveal inflammation of the cavum in 15 patients and of the bone marrow and joint capsule in 1 patient each. CONCLUSION: As visualized by MRI, sacroiliitis in SpA is characterized by involvement of different joint structures. Whereas the iliac and the sacral side of the sacroiliac joints are almost equally affected, the dorsocaudal synovial part of the joint is involved significantly more often than the ventral part, especially in early disease. Sacroiliac enthesitis is not a special feature of early sacroiliac inflammation.