Overview, Vol 13, Issue 11

Only doubt is certain and disbelief worth believing.
Without this courage there can be no learning.
Believe nothing.

"The quarterly journal Progress in Osteoporosis began in October 1993 as Advances in Osteoporosis. Its purpose was to provide readers without easy access to the literature with summaries of the most important literature. We now inhabit a virtual world. Information is instantaneously accessible to all at the tap of a keyboard; understanding is not. In the spirit captured by the anonymous author*, the purpose of this publication is to provide critical evaluation of the most important literature and so to provoke discussion. It is our intention to promote dialogue which examines the quality of information published and so its credibility. The opinions expressed are my own and do not necessarily reflect those of the International Osteoporosis Foundation."

We invite readers to comment on and discuss this journal entry at the bottom of the page.

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Several advances have been made in therapeutics and the most interesting work presented at the 2013 ASBMR Meeting in Baltimore is summarized below. Further work of interest was presented in the previous issue of Progress in Osteoporosis. As always, the interpretation of the data is based on the contents of the abstracts and presentations and must remain tentative until the work has undergone peer review and can be scrutinized when it is in published so that having written “…all your piety nor wit shall lure it back to cancel half a line, nor all your tears blot out a word of it" (Rubaiyat of Omar Khayyam).

PTH and Osteosarcoma
No evidence in human subjects

In rat toxicology studies, teriparatide given for their entire life caused a dose dependent increase in the incidence of osteosarcoma. In adults, the incidence of osteosarcoma is 2.7 cases per million person-years. The third annual linkage included 38 state cancer registries covering 86% of the US population linking 26,810 patients from the Forteo Patient Registry with 1641 adult osteosarcoma cases diagnosed since January 1, 2009. No matches were identified as of December 2012 of the 30,758 registrants. Evaluation of the first 3 years of data detected no signals of a possible association between teriparatide and osteosarcoma (1).

Once Weekly Teriparatide

Sugimoto et al (2) report the antifracture efficacy of weekly teriparatide injection (56.5 mg) in a randomized, double-blind, placebo-controlled trial of 542 Japanese patients with osteoporosis (65-95 years). Incident vertebral fracture occurred in 2.7% (7/261) treated subjects and 13.2% controls (37/281), RR 0.20. Fracture risk reductions were observed in subjects under 75 years (RR 0.06; p=0.007) and over 75 years (RR 0.32; p=0.015), in those with one prevalent vertebral fracture (RR 0.08; p=0.015), in those with >2 vertebral fractures (RR 0.29; p=0.009), in those with grade 3 deformity (RR 0.26; p=0.003), and those with spine lumbar <-2.5SD (RR 0.25; p=0.035).

Human PTHrP Analog

Doyle et al (3) report that BA058, an analog of hPTHrP (1-34), was given 9 months post-OVX for 16 months to aged osteopenic, OVX cynomolgus monkeys >9 years of age at 0.2, 1 or 5 mg/kg. 1 and 5 mg/kg/day reversed OVX-induced osteopenia at the spine with increased yield load of ~50% for the vertebral core and ~20% for the vertebral body compared to OVX controls. These changes were consistent with the increases in BMD of up to ~25%. At 1 and 5 mg/kg/day, BA058 completely restored bone mass and bone strength (yield load) to values comparable to sham control. At 0.2 mg/kg/day, there were partial gains in BMD and strength.

Of interest is a manuscript just published by Horwitz et al (4). The investigators compared 400 or 600 mg/d PTHrP(1-36) and 20 mg/d PTH(1-34) in a 3-month randomized, prospective study of 105 postmenopausal women. The increase in CTX by PTHrP(1-36) (30%) was less than with PTH(1-34) (92%) (p<0.05). The increase in P1NP with PTHrP(1-36) (46% and 87%) was also less than with PTH(1-34) (171%) (p<0.0005). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all groups. Lumbar spine, total hip and femoral neck BMD increased equivalently in each group, but proximal femur values were only significant for the two doses of PTHrP(1-36). PTHrP(1-36) 600 required a dose reduction for hypercalcemia in three subjects. Results of morphology will be of interest when available.

Figure 1. Bone turnover markers. Bars indicate SEM. *,#,†Significance comparing groups. (A) PINP increased in all groups (p<0.0005) and was sustained to 90 days. The increase in PTHrP(1-36) was less than that with PTH(1-34). (B) CTX increased later than PINP, at day 90 in the PTHrP(1-36) groups and day 60 in the PTH(1-34) group. The change at day 90 was less in the PTHrP(1-36) groups than in the PTH(1-34) group (p<0.05). Reproduced from J Bone Miner Res 2013; 28:2266-76 with permission of the American Society of Bone and Mineral Research.



Figure 2. There was no difference in BMD change between groups at any site. Bars indicate SEM. #,†Significance compared baseline values. Lumbar spine BMD increased equivalently and significantly in all groups. Total hip and femoral neck BMD increased equivalently but was significant only for the two PTHrP(1-36) groups (p<0.05 vs. baseline) at the total hip and for the PTHrP(1-36) 400 group at the femoral neck (p<0.05 vs. baseline). There was no change in the forearm BMD in any group. Reproduced from J Bone Miner Res 2013; 28:2266-76 with permission of the American Society of Bone and Mineral Research.

Combining Anabolic Plus Antiresorptive Therapy

This approach to treatment took off with a bad start several years ago with two studies published in the New Engl J Med suggesting that administering an antiresorptive like alendronate (ALN) with PTH produced blunting relative to the effect of PTH alone on BMD and remodeling markers (5,6). The rationale examining this apparent blunting was that the anabolic effect of PTH is in large part remodeling based rather than modeling based. Suppression of remodeling using a bisphosphonate blunted that component of the effect of PTH. The inference made was that the combination is likely to be ineffective in lowering fracture rates or will be less effective than either treatment alone. No studies have been done examining the antifracture efficacy of combined versus either PTH alone or antiresorptive alone and in most studies, changes in BMD or remodeling markers are at best only weakly associated with reduction in fracture risk reported with any drug.

It is unfortunate that the use of combined therapy by stimulating bone formation using PTH and reducing resorption with remodeling suppressants has fallen out of favor because the notion of blunting may be incorrect and it is certainly not observed in most studies. For example, the study by Leder et al combining PTH with a most efficacious resorption inhibitor denosumab (7) challenges this notion, and an earlier study by Cosman et al using zoledronic acid and PTH also suggests this combination produces a better BMD response initially than either treatment alone (8). Several more recent studies support the use of combined therapy.

Whitmarsh et al (9) report changes in cortical mass and thickness from QCT scans 18 months after switching to teriparatide after 12 months prior raloxifene (n=25) or ALN (n=40) vs. 18 months after combining previous raloxifene (n=28) and ALN (n=41) with teriparatide. There was a global mass increase for the add group (2.8% raloxifene, 1.6% ALN) that was greater than switching (0.7% raloxifene, -0.8% ALN) and mainly located at the posterior trochanter. Cortical thickness increased in the combined therapy group (3.7% raloxifene, 1.9% ALN) but no greater or worse than the switch group (1.7% raloxifene, 3.0% ALN).

Figure 3. The mean thickness and mass changes. Reproduced from J Bone Miner Res 28 (Suppl 1) with permission of the American Society of Bone and Mineral Research.









De Bakker et al (10) developed an in vivo dynamic imaging technique to test the hypothesis that combined PTH (60 mg/kg) and ALN (50 mg/kg) increase bone formation and inhibit bone resorption in 3-month-old rats during 12-days. Proximal tibia scans (Scanco vivaCT40) at days 4 and 12 were subtracted to identify formation and resorption sites. Compared to baseline, PTH+ALN caused a greater increase in BV/TV than PTH (45% vs. 33%), 300% greater BFR/BS and 110% greater MAR than vehicle or ALN, while PTH had 300% greater BFR/BS than vehicle. Combined therapy increases bone formation while inhibiting resorption which partially explains the additive effect over monotherapy.

Altman et al (11) hypothesized that combined PTH+ALN (n=9) would result in a greater improvement in trabecular bone structure and strength of the proximal tibia than PTH alone by enhancing bone formation upon trabecular surfaces. Saline (Veh, n=6), PTH (60 mg/kg, n=9), ALN (50 mg/kg, n=6), or both were given daily to 3-month-old rats for 12 days. Scanco vivaCT 40 scans showed PTH caused 7%, 19%, and 33% increase in BV/TV at day 4, 8, and 12. PTH+ALN resulted in 9%, 25%, and 45% increases, respectively. Similar increases in Tb.Th were observed for PTH (7-35%) and PTH+ALN (8-35%). Little or no change in Tb.Th or BV/TV was detected in the Veh and ALN groups. Tb.N showed no difference between groups. SMI suggests a 15% and 27% increase in platelike structures with PTH and PTH+ALN groups, respectively, compared with a 6% increase in the ALN group and no change in the Veh group. At day 12, the PTH+ALN group had 9% and 13% greater BV/TV and platelike structure than the PTH group. Overall, ALN, PTH, and PTH+ALN achieved 25%, 68%, and 103% increases in stiffness, respectively. PTH and PTH+ALN had reduced tissue mineralization (4.5% and 3.0%), possibly due to the new bone formation. The authors report an additive effect of combined PTH and ALN therapy over monotherapy on trabecular microstructure and strength in rats and improvement in SMI. Combined treatment is additive, blunting is not observed in this study.

Antisclerostin Antibody Treatment

PTH molecules are currently the only anabolic therapy we have available for clinical use. There are several concerns. First, there are no studies showing that this drug reduces hip fractures. The pivotal study by Neer et al (12) was stopped due to concerns about the long term safety following the initial report of osteosarcoma in rats. PTH molecules may have anti-hip fracture efficacy, but there is just no data supporting this notion. Second, nonvertebral fracture risk reduction was reported in the pivotal study but this has not been confirmed in the later study using PTH(1-84) and nor in the study of weekly PTH. However, the study by Neer et al was a little less than rigorous regarding the classification of nonvertebral fracture as traumatic or ‘osteoporotic’, a decision left to the investigator. A close look at the types of fractures included as ‘osteoporotic’ makes the veracity of the conclusion tenuous. Third, there is only modest evidence that PTH molecules stimulate periosteal apposition and the biological significance of any periosteal apposition reported using histomorphometry is problematic. Fourth, the anabolic effect is largely remodeling based not modeling based. New bone deposited is mainly found upon crenated surfaces reflecting that most of the anabolic effect occurs upon existing remodeling sites; much less bone formation occurs upon quiescent bone surfaces. This is a limitation because about 80% of the bone surface is quiescent, so the surface available for building bone is vacant land, nothing is happening! Fifth, there is evidence that PTH administration is associated with an increase in intracortical porosity. This may be transitory and, in part, it may be factitious because deposition of new under mineralized bone may be registered by imaging techniques as void rather than ‘bone’ due to attenuation being below the threshold level nominated to represent mineralized bone tissue. Whatever the case, there is a real need for the development of bone forming treatments. The most promising on the horizon are the sclerostin inhibiting molecules.

Increased bone formation may be the result of increased numbers of osteoblasts by activation and differentiation of existing lining cells or the birth of new cells. Ominsky et al (13) investigated if the acute increase in bone formation in response to sclerostin antibody (Scl-Ab) is associated with an increase in RUNX2-positive (RUNX2+) cells adjacent to the cancellous bone surface and in the peritrabecular stroma (osteoprogenitors) in vertebrae from OVX rats following a single dose of Scl-Ab 100 mg/kg (Scl-Ab VI). Despite a 280% and 65% increase in OS/BS and MS/BS, respectively, RUNX2+ cells adjacent to the surface were not increased (Scl-Ab = 269,200±65,293; Veh = 251,600±29,711). The total number of peritrabecular RUNX2+ osteoprogenitor cells was also similar (Scl-Ab = 57,600±9,633; Veh = 60,000±18,547). The acute increase in bone formation following Scl-Ab treatment is not associated with an increase in surface-associated RUNX2+ cells or osteoprogenitor cells but may be mediated by activation of lining cells into matrix-producing osteoblasts.

Genant et al (14) report romosozumab (210 mg QM) stimulated bone formation, decreased bone resorption and increased BMD in 55–85 year old postmenopausal women. In this 12-month phase 2 study vBMD increased at the lumbar spine and total hip compared with placebo and teriparatide (20 mg QD). Trabecular vBMD increased similarly with romosozumab and teriparatide at the lumbar spine? (18.3 vs. 20.1%, respectively), more so with romosozumab at the total hip (10.8 vs. 4.2%). Romosozumab resulted in greater increases in cortical vBMD at the lumbar spine compared with teriparatide (13.7 vs. 5.7%) and greater increases in cortical BMC (23.3 vs. 10.9%). At the total hip, increases in cortical vBMD (1.1%) and BMC (3.4%) were observed with romosozumab but not with teriparatide (perhaps due to issues in segmenting bone at this location). Nevertheless, the data look promising.

Figure 4. Increases at the averaged L1 +2 and total hip following treatment with placebo, PTH and romosozumab. Reproduced from J Bone Miner Res 28 (Suppl 1) with permission of the American Society of Bone and Mineral Research.




Bone Strength

Keaveny et al (15) studied in 42 postmenopausal women mean age 62 years with low aBMD comparing placebo, blosozumab 180 mg every 2 or 4 weeks, or 270 mg every 2 weeks. In the treated groups, there were increases in spine and hip strength at 24 and 52 weeks. At the spine, blosozumab increased strength compared to baseline by up to 29.6 % at week 24 and 37.0% at week 52, and at the hip, blosozumab increased strength by up to 9.6% at week 24, and 12.6% at week 52. At the spine and hip, these strength changes were associated with increases in volumetric BMD of the trabecular and cortical compartments.

Ominsky et al (16) assessed 6-month-old OVX rats at 8 months of age treated with weekly vehicle, or 3, 10, or 50 mg/kg romosozumab for 12 months. Bone mass was dose dependently increased throughout the skeleton. BMD increased by 40% over baseline at the spine and whole femur at the 50 mg/kg/wk dose. At the tibia diaphysis, cortical thickness increased by pQCT at all doses compared to OVX controls, due to changes on periosteal and endocortical surfaces. Romosozumab increased ex vivo bone area and strength at the femur midshaft, neck, and lumbar vertebra at all doses. Peak load was dose dependently increased at the femur midshaft (41-121%), femur neck (33-46%), and vertebra (150-268%). These improvements correlated with bone mass with r2 values of 0.92, 0.41, and 0.94 at the femur shaft, femur neck, and lumbar vertebra, respectively. Material properties at the femur shaft suggested improved ultimate strength and toughness while elastic modulus remained unaffected.


For reasons that are not understood, the effects of anabolic treatment attenuate when treatment is stopped. Ma et al (17) examined maintenance of benefits achieved using Scl-Ab by treating with raloxifene, ALN or a reduced frequency of Scl-Ab administration. Eight month old rats were OVX and allowed to lose bone for 2 months then treatment was started using Scl-Ab, 10mg/kg/week sc for 6 weeks, followed by a) vehicle, b) raloxifene 3 mg/kg/d sc, c) ALN 28 mg/kg/twice a week sc, d) Scl-Ab one injection at week 10. Scl-Ab weekly for 6 weeks restored OVX induced loss in vertebrae and femoral neck and improved strength compared to OVX control. Switching to vehicle or a single Scl-Ab injection resulted in a decline in BMD and strength at all sites. BMD and bone strength gains were largely maintained or slightly increased with raloxifene or ALN at all sites. By the end of the 8-week maintenance period, BMD and bone strength in all groups previously treated with Scl-Ab were still higher than those in the OVX controls, with the exception of the Scl-Ab single injection group, where femoral neck strength declined to a level not different from OVX control.


Robinson et al (18) retreated 8-10 week old BALB/c mice with Scl-Ab and report increases in P1NP that peaks 4 days after dosing and returns to baseline after 7 days. After five doses of Scl-Ab (weekly, 10 mg/kg sc) the peak serum PINP (64 ng/ml) was lower than in age-matched animals dosed with Scl-Ab for the first time (101 ng/ml). An increase in P1NP was observed after each administration of Scl-Ab, but the fifth dose resulted in only 24% increase in P1NP from predose to peak levels measure 4 days later whilst age-matched animals dosed for the first time showed a 130% increase. Mice that had received five doses of Scl-Ab (showing an attenuated P1NP response) were allowed an 8 week interval after which these animals were redosed and produced a P1NP response similar to that in age-matched animals dosed for the first time. Rechallenge can be timed to overcome the attenuated response to Scl-Ab seen after multiple doses. A further 6 doses with Scl-Ab (weekly) again resulted in an attenuated response to Scl-Ab, which was again reversed after a second 8-week period without dosing. Each dosing interval was associated with increases in whole body areal BMD and each dosing interruption resulted in a decline in areal BMD. Thus, continued dosing attenuates the P1NP response but a first-dose level increase in bone formation can be achieved after a period of Scl-Ab discontinuation.

Li et al (19) explored the effects of Scl-Ab retreatment in 7-month-old OVX rats (11 wks post-OVX) treated with vehicle or Scl-Ab (Scl-Ab VI, 5 mg/kg, sc, twice a week) for 12 weeks, followed by vehicle for 12 weeks then one group of Scl-Ab-treated OVX rats received Scl-Ab and the other group received vehicle for 6 weeks. During initial treatment, P1NP increased in the Scl-Ab group at weeks 2 and 4 and returned to OVX control levels at week 10; it then remained at OVX control levels during the withdrawal phase (through week 24). During retreatment, Scl-Ab increases P1NP comparable to that observed after the initial treatment. Lumbar spine BMD increased throughout Scl-Ab treatment and peaked at week 14, two weeks after withdrawal, gradually returning to sham levels at week 24. After 6 weeks of retreatment, BMD increased again to the peak level at week 14. Trabecular (Tb), endocortical (Ec), and periosteal (Ps) bone formation rate (BFR/BS) peaked at week 6 in the Scl-Ab group and then returned to OVX controls at week 24, but Tb and Ec BFR/BS were greater in the Scl-Ab group than OVX controls at week 12. During the retreatment, the increases in Tb and Ec BFR/BS with Scl- Ab were similar to those following initial treatment; there were increases in Ps BFR/BS. For Tb and Ec eroded surface (ES/BS), similar decreases were observed in the Scl-Ab group compared with vehicle during initial and retreatment phases. After treatment withdrawal, Tb ES/BS increased to levels above OVX controls and Ec ES/BS returned to OVX control levels. Retreatment increased bone formation and BMD, and decreased bone resorption, as during initial treatment. Retreatment with Scl-Ab could be a viable way to increase bone mass.

Figure 5. Treatment increases BMD following OVX. There is a decline in BMD and then a decline which is followed by an increase with retreatment (orange triangle). Reproduced from J Bone Miner Res 28 (Suppl 1) with permission of the American Society of Bone and Mineral Research.






Qin et al (20) studied the effects of Scl-Ab treatment following spinal cord injury (SCI). The authors performed complete spinal cord transection in sclerostin knockout (SOST-/-) mice. Eight weeks after SCI, bone loss was observed at the distal femur and proximal tibia in WT mice, no bone loss was observed in SOST-/- mice. Male Wistar rats underwent complete spinal cord transection; 7 days after SCI, the rats were treated with Scl-Ab at 25 mg/kg/week or vehicle for 7 weeks. SCI resulted in decreases in BMD (-25%) and trabecular bone volume (-66%) at the distal femur. Scl-Ab completely prevented the loss of BMD and trabecular bone volume. Tb.Th increased to levels above values for non-SCI controls, and Tb.N tended to be higher than SCI controls. Scl-Ab increased trabecular bone formation. In cultures of bone marrow cells, SCI increased the number of TRAP+ multinucleated cells as well as mRNA levels of osteoclast differentiation markers, and reduced the number of osteoblasts and mRNA levels of the osteoblast differentiation markers. None of these deleterious changes were observed in the Scl-Ab-treated group. Scl-Ab may represent a promising novel approach to mitigate bone loss after SCI.

Zhang et al (21) evaluated the effect of Scl-Ab in a bone loss model from both estrogen deficiency and immobilization (OVX rats with concurrent hindlimb suspension (HLS)). Four-month-old female rats were divided into 7 groups. HLS was introduced 2 weeks after sham and OVX. Scl-Ab (25 mg/kg) or vehicle was injected sc twice weekly for 5 weeks starting at the time of HLS. HLS or OVX alone resulted in loss of trabecular BV/TV, -29% and -71%, respectively, compared to sham control, whereas the OVX+HLS resulted in 87% bone loss. Scl-Ab preserved BV/TV in rats with HLS or OVX and partially prevented trabecular bone loss in rats with OVX plus HLS. Tb.Th increased to similar extent in HLS, OVX and OVX plus HLS rats treated with Scl-Ab. HLS or OVX+HLS was associated with lower stiffness compared with Sham. Scl-Ab prevented the decrease in stiffness due to HLS, OVX or OVX+HLS. Ultimate load was not lower in HLS, OVX or OVX plus HLS as compared with Sham, but it was greater in Scl-Ab-treated HLS or OVX rats as compared with vehicle controls and sham group. Scl-Ab-treated HLS plus OVX showed increased ultimate load, but not significant compared with OVX control.

Osteogenesis Imperfecta

Sinder et al (22) studied the effects of Scl-Ab in osteogenesis imperfecta (OI) in 3 week-old male Brtl/+ mice with dominant OI. Mineralizing surface (MS/BS) and mineral apposition rate (MAR) were quantified. MS/BS increased by about 100% on the posterior periosteal surface and anterior endosteal surface. On the opposing surfaces (posterior endosteal and anterior periosteal) where resorption would be expected to occur, MS/BS was lower (0-38%). Scl-Ab increased MS/BS on these low bone-forming surfaces in both WT and Brtl/+ mice. On high bone-forming surfaces, MAR was marginally elevated (posterior periosteal) or slightly reduced (anterior endosteal). Scl-Ab increased cortical thickness in both the anterior and posterior compartment of Brtl/+. Scl-Ab increased cortical thickness in Brtl/+ and WT mice by activating bone formation on regions of the cortex that typically undergo resorption as part of a modeling drift. These results highlight the ability of Scl-Ab to activate bone formation on quiescent or resorptive surfaces, while maintaining the modeling based bone formation that occurs in rapidly growing animals.

Grafe et al (23) assessed the efficacy of Scl-Ab in growth Crtap-/- mice, a model of recessive OI. One-week-old female Crtap-/- mice were treated for 6 weeks (Scl-Ab VI, 25 mg/kg, sc, twice a week), PBS treated Crtap-/- and WT mice served as controls (n=6/group). After treatment, spines and femurs were analyzed by µCT. At vertebral body L4, treatment improved BV/TV (+141%), Tb.N (+61%) and Tb.Sp (-45%) compared to PBS-treated Crtap-/- mice. Tb.Th was increased by 49% and not different from WT mice. Cortical thickness at the femur midshaft increased by 14%, and at the femur metaphysis, Scl-Ab increased Tb.N (+53%) and BV/TV (+63%), while Tb.Th remained unchanged.

Matrix Composition

Ross et al (24) determined whether Scl-Ab affects mineralization or the rate of matrix maturation in lumbar vertebrae (L2) in a study of 4-5 year old male cynomolgus monkeys treated with vehicle or 30 mg/kg romosozumab once every 2 weeks for 10 weeks. Treatment led to a 2-fold increase in BFR/BS (p=0.009), and a 46% reduction in the eroded surface (p=0.014) and 42% higher trabecular bone volume (p=0.001). The mean global mineralization was 0.8% lower in the treated group (p=0.097). The number of highly mineralized bone pixels was reduced (p=0.035) with only a marginal increase in low density pixels (p=0.092). Bone tissue between 0.5 and 2 weeks old was ~80% mineralized, and the tissue between 2 and 8 weeks old was 90% mineralized compared to the oldest tissue (8 weeks). Even though a larger fraction of the tissue in the treated group was young there was only a small non-significant lowering of mean global mineralization. Treatment did not affect mineralization kinetics despite the elevated bone formation rate.

Glucocorticosteroid-induced Osteoporosis

Achiou et al (25) investigated the effects of the Scl-Ab on the osteocyte in this animal model of glucocorticoid-induced osteoporosis. Thirty male Wistar rats, 4 months old, were randomly assigned to control group subcutaneously injected 5 days a week with vehicle, (M) group subcutaneously injected 5 days a week with 5 mg/kg methylprednisolone and (M+S) group injected with both methylprednisolone and Scl-Ab (Scl-Ab VI, 25 mg/kg/day, twice a week) for 9 weeks. Between the groups, there were no significant differences in mean lacunar area (ranged from 28.5±2.4 to 34.6±3.6 mm2) or mean lacunar density (ranged from 634±37 to 660±63/mm2). Methylprednisolone caused a decrease in osteocyte lacunar occupancy (42 ± 3.8 vs 53 ± 4.1% for C group), that was prevented by Scl-Ab (60±3.2% M+S vs. 42±3.8% for M group). These changes in lacunar occupancy were inversely correlated with the fractional number of apoptotic osteocytes previously reported (r=-0.74; p=0.001). Scl-Ab prevents the decrease in osteocyte lacunar occupancy and the increase in osteocyte apoptosis caused by methylprednisolone treatment in rats.


1. Kellier N, Krohn K, Gilsenan A, et al. Forteo Voluntary Patient Registry: 3-year progress on a prospective osteosarcoma surveillance study. J Bone Miner Res 2013;28 (Suppl 1). Available at http://www.asbmr.org/asbmr-2013-abstract-detail?aid=72190821-7400-4887-9.... Accessed November 25, 2013.

2. Sugimoto T, Shiraki M, Nakano T, et al. Once-weekly teriparatide reduces vertebral fracture risk – Subgroup analysis from the Teriparatide Once Weekly Efficacy Research (TOWER) Trial. J Bone Miner Res 2013;28 (Suppl 1). Available at http://www.asbmr.org/asbmr-2013-abstract-detail?aid=8e222ec4-0e4d-4eaa-b.... Accessed November 25, 2013.

3. Doyle N, Varela A, Smith SY, Guldberg R, Hatttersley G. BA058, a novel human PTHrP analog: Reverses ovariectomy-induced bone loss and strength at the lumbar spine in aged cynomolgus monkeys. J Bone Miner Res 2013;28 (Suppl 1). Available at http://www.asbmr.org/asbmr-2013-abstract-detail?aid=9d2d5cc3-a2eb-49cc-8.... Accessed November 25, 2013.

4. Horwitz MJ, Augustine M, Kahn L, et al. You have free access to this content
A comparison of parathyroid hormone-related protein (1-36) and parathyroid hormone (1-34) on markers of bone turnover and bone density in postmenopausal women: The PrOP study. J Bone Miner Res 2013;28:.2266.

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